NLRP1-dependent activation of Gasdermin D in neutrophils controls cutaneous leishmaniasis.
Michiel Goris, Katiuska Passelli, Sanam Peyvandi, Miriam Díaz-Varela, Oaklyne Billion, Borja Prat-Luri, Benjamin Demarco, Chantal Desponds, Manon Termote, Eva Iniguez, Somaditya Dey, Bernard Malissen, Shaden Kamhawi, Benjamin P Hurrell, Petr Broz, Fabienne Tacchini-Cottier
Author Information
Michiel Goris: Department of Immunobiology, University of Lausanne, Epalinges, Switzerland.
Katiuska Passelli: Department of Immunobiology, University of Lausanne, Epalinges, Switzerland.
Sanam Peyvandi: Department of Immunobiology, University of Lausanne, Epalinges, Switzerland.
Miriam Díaz-Varela: Department of Immunobiology, University of Lausanne, Epalinges, Switzerland.
Oaklyne Billion: Department of Immunobiology, University of Lausanne, Epalinges, Switzerland.
Borja Prat-Luri: Department of Immunobiology, University of Lausanne, Epalinges, Switzerland.
Benjamin Demarco: Department of Immunobiology, University of Lausanne, Epalinges, Switzerland.
Chantal Desponds: Department of Immunobiology, University of Lausanne, Epalinges, Switzerland.
Manon Termote: Department of Immunobiology, University of Lausanne, Epalinges, Switzerland.
Eva Iniguez: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Somaditya Dey: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Bernard Malissen: INSERM, CNRS, Centre D'Immunologie de Marseille-Luminy, Aix-Marseille Université, Marseille, France.
Shaden Kamhawi: Vector Molecular Biology Section, Laboratory of Malaria and Vector Research, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, United States of America.
Benjamin P Hurrell: Department of Immunobiology, University of Lausanne, Epalinges, Switzerland.
Petr Broz: Department of Immunobiology, University of Lausanne, Epalinges, Switzerland.
Fabienne Tacchini-Cottier: Department of Immunobiology, University of Lausanne, Epalinges, Switzerland. ORCID
Intracellular pathogens that replicate in host myeloid cells have devised ways to inhibit the cell's killing machinery. Pyroptosis is one of the host strategies used to reduce the pathogen replicating niche and thereby control its expansion. The intracellular Leishmania parasites can survive and use neutrophils as a silent entry niche, favoring subsequent parasite dissemination into the host. Here, we show that Leishmania mexicana induces NLRP1- and caspase-1-dependent Gasdermin D (GSDMD)-mediated pyroptosis in neutrophils, a process critical to control the parasite-induced pathology. In the absence of GSDMD, we observe an increased number of infected dermal neutrophils two days post-infection. Using adoptive neutrophil transfer in neutropenic mice, we show that pyroptosis contributes to the regulation of the neutrophil niche early after infection. The critical role of neutrophil pyroptosis and its positive influence on the regulation of the disease outcome was further demonstrated following infection of mice with neutrophil-specific deletion of GSDMD. Thus, our study establishes neutrophil pyroptosis as a critical regulator of leishmaniasis pathology.
References
PLoS Pathog. 2017 Feb 13;13(2):e1006196
[PMID: 28192528]
