Infection Immunology (Infection & Immunity)
-
The "Infection & Immunity" group focuses on research into the host response to infection and vaccination in the context of cohort studies in humans with a focus on SARS-CoV2 infections, the human immunodeficiency virus (HIV), oncogenic human papillomaviruses (HPV), Mycobacterium tuberculosis (MTB) and helminth infections (together with AG Inge Kroidl). This includes the molecular characterization of the infectious pathogen, the identification of correlates of immune protection against infection and disease progression, the discovery of biomarkers for TB diagnostics and therapy monitoring, the characterization of HIV reservoirs and the mapping of B-cell epitopes after vaccination. In addition to the analysis of systemic cellular and humoral immune responses, the group has expertise in the analysis of effector cell subsets in human tissue samples using multiplex fluorescence immunohistochemistry in combination with the detection of viral nucleic acids using in situ hybridization to study the microenvironment of virus-infected cells. The ability to bioinformatically analyze large RNA sequencing data and microscopy images is being further expanded.
Immunology laboratory and work areas
In addition to pure research activities, we also offer GCP-compliant laboratory services for partners from the biomedical industry during clinical phase 1 to phase 3 of vaccine studies. This includes the management of investigational medicinal products, the processing of human samples, biobanking and international sample logistics. This includes the processing of blood samples (plasma, serum, isolation of peripheral blood mononuclear cells). The group also has extensive experience in supporting large international clinical trials with a particular focus on Africa. We therefore offer support in sample and reagent logistics, capacity building and the analysis process in various national and international studies. Please contact us for further information.
-
ManagementPD Dr. rer. nat. Christof GeldmacherUnit Head - Research Group "Infection and Immunity"Dr. rer. nat. Kathrin HeldUnit Head - Research Group "Infection and Immunity"TeamMohamed Ahmed, PhDPostdocDr. rer. nat. Olga BaranovBioinformatics ManagerÉäxgeAgpguüqviSm/nful+vfiuyz,iu miNadja Bräuercand. rer. nat.TgmkgsApgifipvim fulrvfiuyziuemiClaudia Bräu-HebergerCTA, ResearchDr. Mkunde ChachagePhD, MSc, NIMR-Mbeya Medical Research Center, TanzaniaTabea Esercand. rer. nat.Luming LinPhD studentMairi McCleanPhD candidateOgl:pl Oyyäiguvimeful#vfiuyziu miDr. rer. nat. Wilbert MbuyaNIMR-Mbeya Medical Research Center, TanzaniaSabine RappeMTLA, ResearchDanni Wang, MSccand. rer. nat.MguulsUguxvim ful+vfiuyziusmiDoctoral, PhD, Master's and Bachelor's studentsIsabel Brandcand. med. n.n.Nadja Bräuercand. rer. nat.Tgmkg-Apgifipvim fulhWvfiuyzWiu-miLeonard Gilbertcand. med. n.n.Augusta Horvathcand. med. n.n.Yuka Nadaicand. med. n.n.Nora Pierothcand. med. n.n.Alumni
Nadia Sitoe, PhD 2023, thesis title: "Inflammatory and prognostic biomarkers associated with pulmonary tuberculosis long-term sequelae after TB treatment in relation to HIV status and lung impairment"
Wilbert Mbuya, PhD 2022, title of the thesis: "Dissecting the Influence of Human Immunodeficiency Virus Type 1 on Human Papilloma Virus Infection, Disease and Immunity"
Caleb Mufong, Gambia, PhD 2022, Title of the thesis: "Defining The Inflammatory Pathway And Prognostic Neutrophil-derived Biomarkers Associated With Pulmonary Morbidity And Long-Term Outcome Of Patients Following TB Therapy"
Astrid Hielscher, Germany, PhD 2020, title of the thesis: "Phylogenetic comparison of plasma- and cell subset derived viral sequences to identify the cellular origin of HIV plasma viremia"
Mohamed Ahmed from Egypt, PhD degree 2019, thesis title: "Exploring sputum independent host biomarkers for detection of Tuberculosis disease and monitoring treatment"
Rebecca Loose, Germany, Bachelor's degree 2017, thesis title: "Assessing novel Bioinformatic approaches for analyses of polychromatic flow cytometry data"
Krutarth Patel, Germany, PhD degree 2017, thesis title: "Development and evaluation of a urine based rapid molecular diagnostic test for pulmonary tuberculosis with potential for point of care: Cape Town cohort"
Mohamed Ahmed from Egypt, Master's degree 2015, thesis title: "Dissecting the dynamics of the Envelope-specific IgG response over the course of HIV infection"
Mkunde Chachage from Tanzania, PhD degree 2013, thesis title: "Immune system modulation by Infections with Helminths and HIV-1: Impact on pathogen-specific T cell responses, regulatory T cells and systemic Immune activation"
Francesco Nicoli from Italy, PhD degree 2013, title of the thesis: "Immunogenicity and immunomodulatory properties of the HIV-1 Tat protein"
Ivy Gloria Mensah from Ghana, PhD student from 2010 to 2014. Graduated September 2014. Thesis title: "Biomarkers for disease progression and treatment; immunological profiles in individuals infected by different species of the Mycobacterium tuberculosis complex in Ghana"
Leigh-Anne Eller from USA, PhD degree 2014, thesis title: "Acute HIV infection in non-subtype B populations: Viral dynamics, laboratory staging and early detection"
Myrna Benninghoff, Germany, PhD degree 2015, thesis title: "Establishment and validation of a molecular worm diagnostic method at the NIMR-MMRC laboratory in Mbeya, Tanzania: Importance of real-time PCR in the diagnosis of worm diseases - evaluation and outlook"
Felicien Moukambi from Gabon, Master's degree 2012, thesis title: "Development and Optimization of a flow cytometry based (TAM-IGRA) method to study phenotypic and functional changes on Mycobacterium tuberculosis-specific T cells in order to identify potential diagnostic markers to discriminate active and latent Tuberculosis"
-
Research technology platforms and laboratory services
Polychromatic flow cytometry and flow cytometric cell sorting for in-depth characterization of human cellsThe laboratory is equipped with a 13-color Beckmann Coulter CytoFLEX flow cytometer and has extensive experience in the flow cytometric analysis of human cells. This includes the characterization of pathogen-specific T cells after in vitro restimulation or by HLA tetramer staining as well as all other cell types in the blood. The laboratory uses the CyTUM-MIH flow cytometry core unit (weblink: http://www.fcfu.mikrobio.med.tum.de/CyTUM-MIH/home) for flow cytometric cell sorting at biosafety level S2 and S3 to enable downstream analysis of DNA and RNA in sorted cells.
Peptide microarray analyses of pathogen-specific antibody reactionsThe laboratory serves as the central peptide array laboratory for the European HIV Vaccine Alliance(http://www.ehv-a.eu/). We use a fully validated peptide microarray assay to map and analyze specific antigenic regions recognized by the antibodies elicited by the vaccine. The technology is suitable for both clinical and preclinical samples. The technology enables reactivity testing against up to 8000 different peptides in triplicate in multiple samples simultaneously. The design of the peptide microarray is carried out in collaboration with Dr. Georgios Pollakis (University of Liverpool, weblink https://www.liverpool.ac.uk/infection-and-global-health/staff/georgios-pollakis/publications/). The downstream bioinformatic analysis of the generated data is well established and can be adapted depending on the research question.
Histological characterization of tissue resident cells in their natural microenvironmentHistological methods provide valuable information about the cells in their natural environment, e.g. about their relative position in the tissue and about cell-cell interactions. To exploit this information, the laboratory has introduced multiplex fluorescence immunohistochemistry for numerous cell markers in combination with the detection of nucleic acids by in situ hybridization. Customizable semi-automated analysis tools have been established for the most common staining panels. Via the Core Facility Bioimaging at the Biomedical Center (BMC)(https://www.bioimaging.bmc.med.uni-muenchen.de/index.html), we have access to various microscopes depending on the application.Transcriptome analysis by RNA sequencingTranscriptome analysis is well established in the laboratory, with bioinformatics workflows developed in-house. A particular focus of our research is the analysis of low abundance cell populations to discover novel biomarkers. We have expertise in high-throughput analysis of whole blood collected in clinical trials and observational studies, as well as RNA sequencing of sorted rare cell populations such as pathogen-specific low-abundance T cells.
Laboratory services, consulting services and international clinical trial logisticsThe laboratory can provide laboratory services for the processing and analysis of human samples for clinical trials in Munich and elsewhere. This includes the processing of blood samples (plasma, serum, peripheral blood mononuclear cell isolation). The group also has extensive experience in supporting large international clinical trials with a particular focus on Africa. We therefore offer support in sample and reagent logistics, capacity building and the analysis process in various national and international studies. Please contact us for further information.
-
Ongoing projects
- Long-term follow-up of the cellular and humoral immune response after SARS-CoV-2 infection
- The 2H study: Influence of HIV and treatment with ART on HPV-specific infection, disease and immunity
- iCTU - HIV
- TTU-HIV: Immune control of HIV-1
- TB-personalized medicine
- RaPaed - WP4 TB Novel Diagnostics in children
- African Cohort Study (AFRICOS), see press release: A look inside: Blood-based biomarkers could facilitate the early detection of incipient tuberculosis in people with HIV, LMU Klinikum, 13.07.2022
- ERASE TB - WP3 TB Novel Diagnostics
- DZIF Maternity Leave Stipend - Transcriptomic profiling of MTB-specific T cells to identify novel biomarkers for Tuberculosis disease progression and outcome
- DZIF Application for investment goods
- DFG Systems Epidemiological analysis of the COVID-19 PANdemic accounting for host-virus interaction and human behavior (SEPAN)
-
The group is closely linked to the international Clinical Trials Unit of the German Center for Infection Research (DZIF) and contributes to sample processing and biobanking for large international clinical trials and observational studies. The group works closely with the NIMR-Mbeya Medical Research Center in Mbeya, Tanzania, and the Instituto Nacional de Saúde in Maputo, Mozambique, as well as with other African research centers to improve the capacity for infectious disease research in endemic areas on the African continent.
-
Most important funding organizations: DZIF, DFG, EU Horizon 2020, EDCTP
-
Publications (selection)
Nucleocapsid-specific T cell responses associate with control of SARS-CoV-2 in the upper airways before seroconversion.
Eser, T.M., Baranov, O., Huth, M. et al.
Nat Commun 14, 2952 (2023). doi: 10.1038/s41467-023-38020-8Therapeutic Efficacy of a VSV-GP-based Human Papilloma Virus Vaccine in a Murine Cancer Model.
Riepler L, Frommelt LS, Wilmschen-Tober S, Mbuya W, Held K, Volland A, von Laer D, Geldmacher C, Kimpel J.
Journal of Molecular Biology, Vol. 435, Issue 13, 2023, 168096, ISSN 0022-2836Impact of Omicron Variant Infection on Assessment of Spike-Specific Immune Responses Using the EUROIMMUN Quan-T-Cell SARS-CoV-2 Assay and Roche Elecsys Anti-SARS-CoV-2-S.
Ahmed MIM, Plank M, Castelletti N, Diepers P, Eser TM, Rubio-Acero R, Norena I, Reinkemeyer C, Zapf D, Hoelscher M, Janke C, Wieser A, Geldmacher C, On Behalf Of The KoCo/Orchestra Study G.
Diagnostics (Basel). 2023; 13.
Systematic comparison of HIV-1 envelope-specific IgG responses induced by different vaccination regimens: Can we steer IgG recognition towards regions of viral vulnerability?
Horvath A, Rogers L, Pollakis G, Baranov O, Pieroth N, Joseph S, Chachage M, Heitzer A, Maganga L, Msafiri F, Joachim A, Viegas E, Eller L-A, Kibuuka H, Rerks-Ngarm S, Pitisuttithum P, Nitayapan S, Dhitavat J, Premsri N, Fidler S, Shattock R J., Robb M L, Weber J, McCormack S, Munseri P J, Lyamuya E, Nilsson C, Kroidl A, Hoelscher M, Wagner R, Geldmacher C, Held K
Front. Immunol, 2023, Jan 09,13. doi: 10.3389/fimmu.2022.1075606Distinct and dynamic activation profiles of circulating dendritic cells and monocytes in mild COVID-19 and after yellow fever vaccination.
Winheim E, Eser T, Deak F, Ahmed MIM, Baranov O, Rinke L, Eisenacher K, Santos-Peral A, Karimzadeh H, Pritsch M, Scherer C, Muenchhoff M, Hellmuth JC, von Bergwelt-Baildon M, Olbrich L, Hoelscher M, Wieser A, Kroidl I, Rothenfusser S, Geldmacher C, Krug AB.
Eur J Immunol. 2023. (IF 6,688)Enhanced spike-specific, but attenuated nucleocapsid-specific T cell responses upon SARS-CoV-2 breakthrough versus non-breakthrough infections.
Ahmed MIM, Diepers P, Janke C, Plank M, Eser TM, Rubio-Acero R, Fuchs A, Baranov O, Castelletti N, Kroidl I, Olbrich L, Bauer B, Wang D, Prelog M, Liese JG, Reinkemeyer C, Hoelscher M, Steininger P, Uberla K, Wieser A, Geldmacher C.
Front Immunol. 2022; 13: 1026473. (IF 8,786).Long-term follow-up on HIV infected and non-infected women with cervical cancer from Tanzania: staging, access to cancer-directed therapies and associated survival in a real-life remote setting.
Glasmeyer L, McHaro RD, Torres L, Lennemann T, Danstan E, Mwinuka N, Judick M, Mueller W, Mbuya W, Holscher M, Lelle R, Geldmacher C, Kroidl A, France JR.
BMC Cancer. 2022; 22: 12. (IF 4,638)Assessment of tuberculosis disease activity in people infected with Mycobacterium tuberculosis and living with HIV: A longitudinal cohort study.
Kroidl I, Ahmed M, Horn S, Polyak C, Esber A, Parikh A,Eller L A, Kibuuka H, Semwogerere M, Mwesigwa B, Naluyima P, Kasumba J M, Maswai J, Owuoth J, Sing'oei V, Rono E, Loose R, Hoelscher M, Ake J, Geldmacher C, on behalf of the AFRICOS Study Group.
eClinicalMedicine 2022;00: 101470. doi:10.1016/j.eclinm.2022.101470The interplay of viral loads, clinical presentation, and serological responses in SARS-CoV-2 - Results from a prospective cohort of outpatient COVID-19 cases.
Puchinger K, Castelletti N, Rubio-Acero R, Geldmacher C, Eser TM, Deák F, Paunovic I, Bakuli A, Saathoff E, von Meyer A, Markgraf A, Falk P, Reich J, Riess F, Girl P, Müller K, Radon K, Guggenbuehl Noller JM, Wölfel R, Hoelscher M, Kroidl I, Wieser A, Olbrich L; KoCo19 study group.
Virology. 2022 Feb 18;569:37-43. doi: 10.1016/j.virol.2022.02.002. Online ahead of print.PMID: 35245784 Free PMC article.Protective immune trajectories in early viral containment of non-pneumonic SARS-CoV-2 infection.
Pekayvaz K, Leunig A, Kaiser R, Joppich M, Brambs S, Janjic A, Popp O, Nixdorf D, Fumagalli V, Schmidt N, Polewka V, Anjum A, Knottenberg V, Eivers L, Wange LE, Gold C, Kirchner M, Muenchhoff M, Hellmuth JC, Scherer C, Rubio-Acero R, Eser T, Deák F, Puchinger K, Kuhl N, Linder A, Saar K, Tomas L, Schulz C, Wieser A, Enard W, Kroidl I, Geldmacher C, von Bergwelt-Baildon M, Keppler OT, Munschauer M, Iannacone M, Zimmer R, Mertins P, Hubner N, Hoelscher M, Massberg S, Stark K, Nicolai
L.Nat Commun. 2022 Feb 23;13(1):1018. doi: 10.1038/s41467-022-28508-0.PMID: 35197461 Free PMC article.SARS-CoV-2 Beta variant infection elicits potent lineage-specific and cross-reactive antibodies.
Reincke SM, Yuan M, Kornau HC, Corman VM, van Hoof S, Sánchez-Sendin E, Ramberger M, Yu W, Hua Y, Tien H, Schmidt ML, Schwarz T, Jeworowski LM, Brandl SE, Rasmussen HF, Homeyer MA, Stöffler L, Barner M, Kunkel D, Huo S, Horler J, von Wardenburg N, Kroidl I, Eser TM, Wieser A, Geldmacher C, Hoelscher M, Gänzer H, Weiss G, Schmitz D, Drosten C, Prüss H, Wilson IA, Kreye J.
Science. 2022 Feb 18;375(6582):782-787. doi: 10.1126/science.abm5835. Epub 2022 Jan 25.PMID: 35076281HPV Type Distribution in HIV Positive and Negative Women With or Without Cervical Dysplasia or Cancer in East Africa.
Mcharo R, Lennemann T, France J, Torres L, Garí M, Mbuya W, Mwalongo W, Mahenge A, Bauer A, Mnkai J, Glasmeyer L, Judick M, Paul M, Schroeder N, Msomba B, Sembo M, Chiwerengo N, Hoelscher M, Geisenberger O, Lelle RJ, Saathoff E, Maboko L, Chachage M, Kroidl A, Geldmacher C.
Front Oncol. 2021 Nov 30;11:763717. doi: 10.3389/fonc.2021.763717. eCollection 2021.PMID: 34917506 Free PMC article.Major Neutrophil-Derived Soluble Mediators Associate With Baseline Lung Pathology and Post-Treatment Recovery in Tuberculosis Patients.
Muefong CN, Owolabi O, Donkor S, Charalambous S, Mendy J, Sey ICM, Bakuli A, Rachow A, Geldmacher C, Sutherland JS.
Front Immunol. 2021 Nov 23;12:740933. doi: 10.3389/fimmu.2021.740933. eCollection 2021.PMID: 34887853 Free PMC article.Depletion of Human Papilloma Virus E6- and E7-Oncoprotein-Specific T-Cell Responses in Women Living With HIV.
Mbuya W, Held K, Mcharo RD, Haule A, Mhizde J, Mnkai J, Mahenge A, Mwakatima M, Sembo M, Mwalongo W, Agrea P, Hoelscher M, Maboko L, Saathoff E, Geisenberger O, Rwegoshora F, Torres L, Koup RA, Kroidl A, Chachage M, Geldmacher C.
Front Immunol. 2021 Oct 25;12:742861. doi: 10.3389/fimmu.2021.742861. eCollection 2021.PMID: 34759925 Free PMC article.Neutrophils contribute to severity of tuberculosis pathology and recovery from lung damage pre- and post-treatment.
Nwongbouwoh Muefong C, Owolabi O, Donkor S, Charalambous S, Bakuli A, Rachow A, Geldmacher C, Sutherland JS.
Clin Infect Dis. 2021 Aug 24:ciab729. doi: 10.1093/cid/ciab729. Online ahead of print.PMID: 34427644Stepwise Conformational Stabilization of a HIV-1 Clade C Consensus Envelope Trimer Immunogen Impacts the Profile of Vaccine-Induced Antibody Responses.
Hauser A, Carnell G, Held K, Sulbaran G, Tischbierek N, Rogers L, Pollakis G, Tonks P, Hoelscher M, Ding S, Sanders RW, Geldmacher C, Sattentau Q, Weissenhorn W, Heeney JL, Peterhoff D, Wagner R.
Vaccines(Basel). 2021 Jul 6;9(7):750. doi: 10.3390/vaccines9070750.PMID: 34358165 Free PMC article.Cross-reactivity of a pathogenic autoantibody to a tumor antigen in GABAA receptor encephalitis.
Brändle SM, Cerina M, Weber S, Held K, Menke AF, Alcalá C, Gebert D, Herrmann AM, Pellkofer H, Gerdes LA, Bittner S, Leypoldt F, Teegen B, Komorowski L, Kümpfel T, Hohlfeld R, Meuth SG, Casanova B, Melzer N, Beltrán E, Dornmair K. Proc Natl
Acad Sci U S A. 2021HIV DNA reservoir and elevated PD-1 expression of CD4 T-cell subsets particularly persist in the terminal ileum of HIV-positive patients despite cART.
Horn C, Augustin M, Ercanoglu MS, Heger E, Knops E, Bondet V, Duffy D, Chon SH, Nierhoff D, Oette M, Schäfer H, Vivaldi C, Held K, Anderson J, Geldmacher C, Suárez I, Rybniker J, Klein F, Fätkenheuer G, Müller-Trutwin M, Lehmann C.
HIV Med. 2021Flow cytometric analysis of cell lineage and immune activation markers using minimal amounts of human whole blood-Field method for remote settings.
Horn S, Ahmed MIM, Geldmacher C, Marandu TF, Osei-Mensah J, Debrah A, Layland LE, Hoerauf A, Kroidl I.
JImmunol Methods. 2021CD34T+ Humanized Mouse Model to Study Mucosal HIV-1 Transmission and Prevention.
Vanshylla K, Held K, Eser TM, Gruell H, Kleipass F, Stumpf R, Jain K, Weiland D, Münch J, Grüttner B, Geldmacher C, Klein F.
Vaccines(Basel). 2021Serological Protection 5-6 Years Post Vaccination Against Yellow Fever in African Infants Vaccinated in Routine Programs.
Idoko OT, Domingo C, Tapia MD, Sow SO, Geldmacher C, Saathoff E, Kampmann B.
Front Immunol. 2020Depletion and activation of mucosal CD4 T cells in HIV infected women with HPV-associated lesions of the cervix uteri.
Mbuya W, Mcharo R, Mhizde J, Mnkai J, Mahenge A, Mwakatima M, Mwalongo W, Chiwerengo N, Hölscher M, Lennemann T, Saathoff E, Rwegoshora F, Torres L, Kroidl A, Geldmacher C, Held K, Chachage M.
PLoS One. 2020Induction of Identical IgG HIV-1 Envelope Epitope Recognition Patterns After Initial HIVIS-DNA/MVA-CMDR Immunization and a Late MVA-CMDR Boost.
Joachim A, Ahmed MIM, Pollakis G, Rogers L, Hoffmann VS, Munseri P, Aboud S, Lyamuya EF, Bakari M, Robb ML, Wahren B, Sandstrom E, Nilsson C, Biberfeld G, Geldmacher C and Held K.
Front. Immunol. 2020Wuchereria bancrofti infection is linked to systemic activation of CD4 and CD8 T cells.
Kroidl I, Chachage M, Mnkai J, Nsojo A, Berninghoff M, Verweij JJ, Maganga L, Ntinginya NE, Maboko L, Clowes P, Hoelscher M, Saathoff E and Geldmacher C.
PLoS Negl Trop Dis. 2019Envelope-specific epitope recognition patterns of HIV vaccine-induced IgG antibodies are linked to immunogen structure and sequence.
Nadai Y, Held K, Joseph S, Ahmed MIM, Hoffmann VS, Peterhoff D, Missanga M, Bauer A, Joachim A, Reimer U, Zerweck J, McCormack S, Cope AV, Tatoud R, Shattock RJ, Robb ML, Sandstroem EG, Hoelscher M, Maboko L, Bakari M, Kroidl A, Wagner R, Weber J, Pollakis G, Geldmacher C.
Front Immunol. 2019Communication of CD8 + T Cells With Mononuclear Phagocytes in Multiple Sclerosis.
Kojevic Sabolek M, Held K, Beltrán E, Niedl AG, Meinl E, Hohlfeld R, Lassmann H, Dornmair K
Ann Clin Transl Neurol. 2019Phenotypic Changes on Mycobacterium Tuberculosis-Specific CD4 T Cells as Surrogate Markers for Tuberculosis Treatment Efficacy.
Ahmed MIM, Ntinginya NE, Kibiki G, Mtafya BA, Semvua H, Mpagama S, Mtabho C, Saathoff E, Held K, Loose R, Kroidl I, Chachage M, von Both U, Haule A, Mekota AM, Boeree MJ, Gillespie SH, Hoelscher M, Heinrich N, Geldmacher C.
Front Immunol. 2018Preferential Targeting of Conserved Gag Regions after Vaccination with a Heterologous DNA prime-Modified Vaccinia Ankara (MVA) boost HIV-1 vaccine regimen.
Bauer A, Podola L, Mann P, Missanga M, Haule A, Sudi L, Nilsson C, Kaluwa B, Lueer C, Mwakatima M, Munseri PJ, Maboko L, Robb ML, Tovanabutra S, Kijak G, Marovich M, McCormack S, Joseph S, Lyamuya E, Wahren B, Sandström E, Biberfeld G, Hoelscher M, Bakari M, Kroidl A, Geldmacher C.
J Virol. 2017Effect of Wuchereria bancrofti infection on HIV incidence in southwest Tanzania: a prospective cohort study.
Kroidl I, Saathoff E, Maganga L, Makunde WH, Hoerauf A, Geldmacher C, Clowes P, Maboko L, Hoelscher M.
Lancet. 2016CD25+ FoxP3+ Memory CD4 T Cells Are Frequent Targets of HIV Infection In Vivo.
Chachage M, Pollakis G, Kuffour EO, Haase K, Bauer A, Nadai Y, Podola L, Clowes P, Schiemann M, Henkel L, Hoffmann D, Joseph S, Bhuju S, Maboko L, Sarfo FS, Eberhardt K, Hoelscher M, Feldt T, Saathoff E, Geldmacher C.
JVirol. 2016CTLA4 as Immunological Checkpoint in the Development of Multiple Sclerosis.
Gerdes LA*, Held K*, Beltran E*, Berking C, Prinz JC, Junker A, Tietze JK, Ertl-Wagner B, Straube A, Kuempfel T, Dornmair K*, Hohlfeld R*
Ann Neurol. 2016Commentary: First-in-human trial of a live-attenuated Mycobacterium tuberculosis vaccine.
Geldmacher C, Hatherill M.
Lancet Respir Med. 2015Commentary: Early Identification of Progressive TB Disease Using Host Biomarkers.
Rachow A, Heinrich N, Geldmacher C
EBioMedicine. 2015αβ T-cell receptors from multiple sclerosis brain lesion show MAIT cell-reladed features.
Held K, Bhonsle-Deeng L, Siewert K, Sato W, Beltrán E, Schmidt S, Rühl G, Ng JKM, Engerer P, Moser M, Klinkert WEF, Babbe H, Misgeld T, Wekerle H, Laplaud DA, Hohlfeld R, Dornmair K
Neurol N2. 2015Assessment of the novel T-cell activation marker-tuberculosis assay for diagnosis of active tuberculosis in children: a prospective proof-of-concept study.
Portevin D, Moukambi F, Clowes P, Bauer A, Chachage M, Ntinginya NE, Mfinanga E, Said K, Haraka F, Rachow A, Saathoff E, Mpina M, Jugheli L, Lwilla F, Marais BJ, Hoelscher M, Daubenberger C, Reither K*, Geldmacher C*.
LancetInfect Dis. 2014Helminth-Associated Systemic Immune Activation and HIV Co-receptor Expression: Response to Albendazole/Praziquantel Treatment.
Chachage M, Podola L, Clowes P, Nsojo A, Bauer A, Mgaya O, Kowour D, Froeschl G, Maboko L, Hoelscher M, Saathoff E, Geldmacher C.
PLoS Negl Trop Dis. 2014Interaction between HIV and Mycobacterium tuberculosis: HIV-1-induced CD4 T-cell depletion and the development of active tuberculosis.
Geldmacher C, Zumla A, Hoelscher M.
Curr Opin HIV AIDS. 2012Pathogen-specific T cell depletion and reactivation of opportunistic pathogens in HIV infection.
Geldmacher C, Koup RA.
Trends Immunol. 2012 May;33(5):207-14Expression of herpes simplex virus 1-encoded microRNAs in human trigeminal ganglia and their relation to local T-cell infiltrates.
Held K, Junker A, Dornmair K, Meinl E, Sinicina I, Brandt T, Theil D, Derfuss T
JVirol. 2011Preferential infection and depletion of Mycobacterium tuberculosis-specific CD4 T cells after HIV-1 infection.
Geldmacher C, Ngwenyama N, Schuetz A, Petrovas C, Reither K, Heeregrave EJ, Casazza JP, Ambrozak DR, Louder M, Ampofo W, Pollakis G, Hill B, Sanga E, Saathoff E, Maboko L, Roederer M, Paxton WA, Hoelscher M, Koup RA.
JExp Med. 2010Minor viral and host genetic polymorphisms can dramatically impact the biologic outcome of an epitope-specific CD8 T-cell response.
Geldmacher C, Metzler IS, Tovanabutra S, Asher TE, Gostick E, Ambrozak DR, Petrovas C, Schuetz A, Ngwenyama N, Kijak G, Maboko L, Hoelscher M, McCutchan F, Price DA, Douek DC, Koup RA.
Blood. 2009SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection.
Petrovas C, Price DA, Mattapallil J, Ambrozak DR, Geldmacher C, Cecchinato V, Vaccari M, Tryniszewska E, Gostick E, Roederer M, Douek DC, Morgan SH, Davis SJ, Franchini G, Koup RA.
Blood. 2007CD8 T-cell recognition of multiple epitopes within specific Gag regions is associated with maintenance of a low steady-state viremia in human immunodeficiency virus type 1-seropositive patients.
Geldmacher C, Currier JR, Herrmann E, Haule A, Kuta E, McCutchan F, Njovu L, Geis S, Hoffmann O, Maboko L, Williamson C, Birx D, Meyerhans A, Cox J, Hoelscher M.
JVirol. 2007 -
News
-
Infection & Immunity working group - Research Interests
The "Infection & Immunity" work group concentrates on dissecting the host response to infection and vaccination during human cohort studies with primary focus on SARS-CoV2 infection, the Human Immunodeficiency Virus (HIV), oncogenic Human Papilloma Viruses (HPV), Mycobacterium tuberculosis (MTB) and helminth infections (together with AG Inge Kroidl). This includes the molecular characterization of the infecting pathogen, identification of correlates of immune protection from infection and disease progression, biomarker discovery for TB diagnostics and treatment monitoring, characterization of HIV reservoirs, as well as mapping of B cell epitopes upon vaccination. Besides the analysis of systemic cellular and humoral immune responses, the group has proficiency in the analysis of effector cell subsets in human tissue samples using multiplex fluorescence immunohistochemistry combined with detection of viral nucleic acids using in situ hybridization to study the micro-environment of virus-infected cells. The capacity for bioinformatic analysis of large-scale RNA sequencing data and microscopy images is undergoing further development.
The working group is closely affiliated with the international Clinical Trials Unit from the German Center for Infection Research (DZIF) and contributes to human subject specimen processing and biobanking during large international clinical trials and observational studies. The group collaborates closely with the NIMR-Mbeya Medical Research Center in Mbeya, Tanzania and the Instituto Nacional da Saude in Maputo, Mozambique as well as other African Research Centers to support improving the capacity for infectious disease research in endemic settings on the African continent.
Besides pure research activities, we also offer GCP conform laboratory services to partners from the biomedical industry during clinical phase 1 to phase 3 vaccine trials. This includes management of investigational medical products, human sample processing, biobanking and international sample logistics.
Research Technology Platforms and Laboratory services
Platform: Polychromatic flow cytometry and flow cytometric cell sorting for in-depth characterization of human cellsThe laboratory is equipped with a 13-colour Beckmann Coulter CytoFLEX Flow Cytometer and has vast experience in the flow cytometric analysis of human cells. This includes characterization of pathogen-specific T cells after in vitro restimulation or by HLA tetramer staining as well as any other cell type in the blood. The laboratory uses the Flow Cytometry core unit CyTUM-MIH for flow cytometric cell sorting at biosafety S2 and S3 level to allow for downstream analyses of DNA and RNA in sorted cells.
Platform: Peptide microarray analyses of pathogen-specific antibody responsesThe laboratory serves as a core peptide array laboratory for the European HIV Vaccine Alliance. We use a fully validated peptide microarray assay to map and analyse specific antigenic regions recognized by antibodies elicited by vaccination. The technology is established for both, clinical and preclinical specimen. The technology allows reactivity testing against up to 8000 different peptides in triplicates in multiple samples simultaneously. Custom design of the peptide microarray is performed in collaboration with Dr. Georgios Pollakis(University of Liverpool). Bioinformatic downstream analysis of generated data is well established and can be adapted depending on the research question.
Platform: Histological characterization of tissue-resident cells in their natural microenvironmentHistological techniques provide valuable information on cells within their natural environment, such as their relative positioning within the tissue and cell-cell interactions. To take advantage of this information, the laboratory has established multiplex fluorescence immunohistochemistry for numerous cell markers in combination with the detection of nucleic acids using in situ hybridization. Customizable semi-automated analysis tools are established for the most common staining panels. We have access to various microscopes via the Core Facility Bioimaging at the Biomedical Center (BMC), depending on the application in question.
Platform: Transcriptome analysis by RNA sequencingTranscriptome analysis is well established within the lab, with bioinformatic workflows developed in house. A particular focus of our research includes the analysis of low abundant cell populations for the discovery of novel biomarkers. We have expertise in high-throughput analysis of whole blood collected in clinical trials and observational studies as well as in low-input RNA sequencing of sorted rare cell populations such as pathogen-specific T cells.
Laboratory services, Consultancies and international clinical study logisticsThe laboratory can provide laboratory services for human sample processing and analysis for clinical studies in Munich and elsewhere. This includes the processing of blood samples (Plasma, Serum, Isolation of Peripheral Blood Mononuclear Cells). The group also has tremendous experience in supporting large international clinical with a specific emphasis on Africa. We therefore provide support on sample and reagent logistics, capacity development and the analytic process in multiple national and international study set ups. Please contact us for more information.