title: Cytokines and microbicidal molecules regulated by IL-32 in THP-1-derived human macrophages infected with New World Leishmania species.
abstract: Interleukin-32 (IL-32) is expressed in lesions of patients with American Tegumentary Leishmaniasis (ATL), but its precise role in the disease remains unknown.
  
  
  
  In the present study, silencing and overexpression of IL-32 was performed in THP-1-derived macrophages infected with Leishmania (Viannia) braziliensis or L. (Leishmania) amazonensis to investigate the role of IL-32 in infection. We report that Leishmania species induces IL-32γ, and show that intracellular IL-32γ protein production is dependent on endogenous TNFα. Silencing or overexpression of IL-32 demonstrated that this cytokine is closely related to TNFα and IL-8. Remarkably, the infection index was augmented in the absence of IL-32 and decreased in cells overexpressing this cytokine. Mechanistically, these effects can be explained by nitric oxide cathelicidin and β-defensin 2 production regulated by IL-32.
  
  
  
  Thus, endogenous IL-32 is a crucial cytokine involved in the host defense against Leishmania parasites.
authors.affiliation: Department of Internal Medicine and Radboud Center of Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.|Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Brazil.
authors.forename: Jéssica Cristina
authors.initials: JC
authors.lastname: Dos Santos
authors.affiliation: Department of Internal Medicine and Radboud Center of Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: Heinhuis
authors.affiliation: Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Brazil.
authors.forename: Rodrigo Saar
authors.initials: RS
authors.lastname: Gomes
authors.affiliation: Department of Internal Medicine and Radboud Center of Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Michelle S M A
authors.initials: MS
authors.lastname: Damen
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, Brazil.
authors.forename: Fernando
authors.initials: F
authors.lastname: Real
authors.affiliation: Departamento de Microbiologia, Imunologia e Parasitologia, Escola Paulista de Medicina, Universidade Federal de São Paulo, Brazil.
authors.forename: Renato A
authors.initials: RA
authors.lastname: Mortara
authors.affiliation: Department of Internal Medicine and Radboud Center of Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Samuel T
authors.initials: ST
authors.lastname: Keating
authors.affiliation: Department of Internal Medicine and Radboud Center of Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.|School of Medicine, Division of infectious diseases, University of Colorado Denver, Aurora, Colorado, United States of America.
authors.forename: Charles A
authors.initials: CA
authors.lastname: Dinarello
authors.affiliation: Department of Internal Medicine and Radboud Center of Infectious Diseases (RCI), Radboud University Medical Center, Nijmegen, The Netherlands.
authors.forename: Leo A B
authors.initials: LA
authors.lastname: Joosten
authors.affiliation: Instituto de Patologia Tropical e Saúde Pública, Universidade Federal de Goiás, Goiânia, Brazil.
authors.forename: Fátima
authors.initials: F
authors.lastname: Ribeiro-Dias
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000378:metabolism; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism*; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006801:Humans; D007378:Interleukins / Q000378:metabolism*; D007892:Leishmania braziliensis / Q000276:immunology*; D007894:Leishmania mexicana / Q000276:immunology*; D008264:Macrophages / Q000276:immunology* / Q000469:parasitology*; D009569:Nitric Oxide / Q000378:metabolism; D023083:beta-Defensins / Q000378:metabolism; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D016207:Cytokines; C106641:DEFB4A protein, human; C496971:IL32 protein, human; D007378:Interleukins; D023083:beta-Defensins; D009569:Nitric Oxide; D054804:Cathelicidins