Immunology and infectious diseases

Pathogenic microorganisms are a global major health threat that is alarmingly aggravated by the drastic increase in multidrug resistance in recent years. Our research focuses on cell-mediated immune mechanisms that restrict microbial infections. We recently discovered that the immune serine proteases of cytotoxic T and natural killer cells, the granzymes, exhibit potent antimicrobial activity by cleaving multiple vital protein substrates triggering rapid microbial death. We, thus, defined a novel immunological paradigm suggesting a crucial role of cytotoxic effector proteases in the immune defence against pathogenic microorganisms (Cell, 2014; Nature Medicine, 2016). Comprehensive proteomics and bioinformatics analysis of bacterial granzyme B substrates in the model pathogen Listeria monocytogenes revealed a highly targeted attack on protein networks that are up-regulated during infectious growth in vivo. This finding suggests an unexpected immune mechanism that specifically targets bacterial proteins directly related to virulence and pathogenicity. We will explore this recently discovered immune strategy by dissecting an evolutionarily conserved host-pathogen interaction, i.e. the immune proteases targeted destruction of proteins in clinically relevant pathogenic bacteria using well-established proteomics as well as bioinformatics tools. These data will provide an evolutionary insight of how to effectively kill bacterial pathogens and restrict infections. Malaria remains one of the most challenging health problems in developing countries. Plasmodium spp., the cause of malaria, have a complex life cycle. However, it is accepted that the exponential growth of the parasites in the blood is responsible for almost all the clinical symptoms of malaria and the associated morbidity and mortality. Therefore, to efficiently prevent malaria pathogenesis and progression toward severe disease, tight control of parasitemia is essential. In collaboration with Dr. Pierre-Yves Mantel, we plan to identify the cytotoxic lymphocyte populations capable to restrict the growth of Plasmodium in red blood cells and characterize the underlying mechanisms. Our preliminary data clearly indicate that the granzymes contribute crucially to the observed growth restriction in red blood cells. Therefore, we also aim to identify the molecular targets of the immune proteases in stage-specific proteomics screens.

Members

Publications

Granulysin Antimicrobial Activity Promotes Dormancy in Mycobacterium tuberculosis
Elirehema Mfinanga, Frederick Haraka, Jan M. Schmidt, Damien Portevin, Erin F. McCaffrey, Max Mpina, Ainhoa Arbués, Mohamed Sasamalo, Owais Abdul Hameed, Sébastien Gagneux, Hellen Hiza, Jacques Fellay, Klaus Reither, José M. Carballido, Anneth Tumbo, Michael Walch, Sarah Schmidiger, Jerry Hella, European Journal of Immunology (2025) | Journal article

Plasmodium falciparum subverts neutrophil function via host miR-451a loaded extracellular vesicles driving bacterial superinfection susceptibility
Simone Lucchesi, Michael Walch, Rickard Sandberg, Kehinde Adebayo Babatunde, Daniel Irimia, Bibin Subramanian, Alex Hopke, Francesco Santoro, Paola Martinez Murillo, Giorgio Montesi, Maria Novedrati, Pierre-Yves Mantel, Michael Hagemann-Jensen, Luis Filgueira, Mtakai Ngara, (2025) | Preprint

Executioner caspases degrade essential mediators of pathogen-host interactions to inhibit growth of intracellular Listeria monocytogenes
Dieter Kressler, Marilyne Lavergne, Alessandro Failla, Safaa Bouheraoua, Patricia Matthey, Sara De Grandis, Oluwadamilola Adenuga, Michael Stumpe, Tanja Muralt, Tiffany Schaerer, Michael Walch, Léa Chèvre, Raffael Schaerer, Pierre-Yves Mantel, Cell Death & Disease (2025) | Journal article

Granulysin antimicrobial activity promotes dormancy inMycobacterium tuberculosis
Erin F. McCaffrey, José M. Carballido, Michael Walch, Sébastien Gagneux, Hellen Hiza, Owais Abdul Hameed, Jacques Fellay, Sarah Schmidiger, Jerry Hella, Jan M. Schmidt, Elirehema Mfinanga, Damien Portevin, Mohamed Sasamalo, Ainhoa Arbués, Anneth Tumbo, Frederick Haraka, Klaus Reither, Max Mpina, (2024) | Preprint

Executioner caspases degrade essential mediators of pathogen-host interactions to inhibit growth of intracellular Listeria monocytogenes
Tiffany Schaerer, Raffael Schaerer, Michael Walch, Oluwadamilola Adenuga, Sara De Grandis, Marilyne Lavergne, Safaa Bouheraoua, Patricia Matthey, Alessandro Failla, Michael Stumpe, Tanja Muralt, Dieter Kressler, Pierre-Yves Mantel, Léa Chèvre, (2024) | Preprint

Biocompatible Rhamnolipid Self‐Assemblies with pH‐Responsive Antimicrobial Activity
Michael Walch, Samuel Watts, Jules D. P. Valentin, Linda Hong, Parth Kadakia, Owais Abdul Hameed, Stefan Salentinig, Advanced Healthcare Materials (2024) | Journal article

Validation of Effective Extracellular Vesicles Isolation Methods Adapted to Field Studies in Malaria Endemic Regions
Matteo Zoia and Bibin Yesodha Subramanian and Klara Kristin Eriksson and Meera Sruthi Ravi and Shekoofeh Yaghmaei and Isabelle Fellay and Brigitte Scolari and Michael Walch and Pierre-Yves Mantel, Frontiers in Cell and Developmental Biology (2022) | Journal article

Improved Purification of Human Granzyme A/B and Granulysin Using a Mammalian Expression System
Valerio Rasi and Owais Abdul Hameed and Patricia Matthey and Sibes Bera and Duane P. Grandgenett and Stefan Salentinig and Michael Walch and Daniel F. Hoft, Frontiers in Immunology (2022) | Journal article

Editorial: The Role of Reactive Oxygen Species in Protective Immunity
Denis Martinvalet and Michael Walch, Frontiers in Immunology (2022) | Journal article

Reactive Oxygen Species: Do They Play a Role in Adaptive Immunity?
Esen Yonca Bassoy and Michael Walch and Denis Martinvalet, Frontiers in Immunology (2021) | Journal article

Oxidative and Non-Oxidative Antimicrobial Activities of the Granzymes
Marilyne Lavergne and Maria Andrea Hernández-Castañeda and Pierre-Yves Mantel and Denis Martinvalet and Michael Walch, Frontiers in Immunology (2021) | Journal article

Granzyme A Produced by γ9δ2 T Cells Activates ER Stress Responses and ATP Production, and Protects Against Intracellular Mycobacterial Replication Independent of Enzymatic Activity
Valerio Rasi and David C. Wood and Christopher S. Eickhoff and Mei Xia and Nicola Pozzi and Rachel L. Edwards and Michael Walch and Niels Bovenschen and Daniel F. Hoft, Frontiers in Immunology (2021) | Journal article

A Profound Membrane Reorganization Defines Susceptibility of Plasmodium falciparum Infected Red Blood Cells to Lysis by Granulysin and Perforin
Maria Andrea Hernández-Castañeda and Marilyne Lavergne and Pierina Casanova and Bryan Nydegger and Carla Merten and Bibin Yesodha Subramanian and Patricia Matthey and Nils Lannes and Pierre-Yves Mantel and Michael Walch, Frontiers in Immunology (2021) | Journal article

γδ T Cells Kill Plasmodium falciparum in a Granzyme- and Granulysin-Dependent Mechanism during the Late Blood Stage
Maria Andrea Hernández-Castañeda and Katharina Happ and Filippo Cattalani and Alexandra Wallimann and Marianne Blanchard and Isabelle Fellay and Brigitte Scolari and Nils Lannes and Smart Mbagwu and Benot Fellay and Luis Filgueira and Pierre-Yves Mantel and Michael Walch, The Journal of Immunology (2020) | Journal article

Granzyme B Attenuates Bacterial Virulence by Targeting Secreted Factors
Diego López León and Patricia Matthey and Isabelle Fellay and Marianne Blanchard and Denis Martinvalet and Pierre-Yves Mantel and Luis Filgueira and Michael Walch, iScience (2020) | Journal article

Role of Extracellular Vesicles in Cellular Cross Talk in Malaria
Kehinde Adebayo Babatunde and Bibin Yesodha Subramanian and Ambroise Dioum Ahouidi and Paola Martinez Murillo and Michael Walch and Pierre-Yves Mantel, Frontiers in Immunology (2020) | Journal article

Human Microglia Respond to Malaria-Induced Extracellular Vesicles
Smart Ikechukwu Mbagwu and Nils Lannes and Michael Walch and Luis Filgueira and Pierre-Yves Mantel, Pathogens (2019) | Journal article

Gamma Delta T Cells and Its Interactions with Extracellular Vesicles during Malaria
Smart Mbagwu and Luis Filgueira and Michael Walch and Pierre-Yves Mantel, The FASEB Journal (2019) | Journal article

Malaria infected red blood cells release small regulatory RNAs through extracellular vesicles
Kehinde Adebayo Babatunde and Smart Mbagwu and María Andrea Hernández-Castañeda and Swamy R. Adapa and Michael Walch and Luis Filgueira and Laurent Falquet and Rays H. Y. Jiang and Ionita Ghiran and Pierre-Yves Mantel, Scientific Reports (2018) | Journal article

Malaria derived extracellular vesicles inhibit neutrophils ROS production and NETs formation
Kehinde Adebayo Babatunde and Michael Walch and Isabel Fellay and Solange Kharoubi-Hess and Luis Filgueira and Ionita Ghiran and Pierre-Yves Mantel, The FASEB Journal (2018) | Journal article

Evaluation of Extracellular Vesicle Function During Malaria Infection
María Andrea Hernández-Castañeda and Smart Mbagwu and Kehinde Adebayo Babatunde and Michael Walch and Luis Filgueira and Pierre-Yves Mantel, Journal of Visualized Experiments (2018) | Journal article

Silver-nanoparticles increase bactericidal activity and radical oxygen responses against bacterial pathogens in human osteoclasts
Valerie Aurore and Fabienne Caldana and Marianne Blanchard and Solange Kharoubi Hess and Nils Lannes and Pierre-Yves Mantel and Luis Filgueira and Michael Walch, Nanomedicine: Nanotechnology, Biology and Medicine (2018) | Journal article