title: IFN-γ-Dependent Recruitment of CD4(+) T Cells and Macrophages Contributes to Pathogenesis During Leishmania amazonensis Infection.
abstract: Interferon gamma (IFN-γ) is a key factor in the protection of hosts against intracellular parasites. This cytokine induces parasite killing through nitric oxide and reactive oxygen species production by phagocytes. Surprisingly, during Leishmania amazonensis infection, IFN-γ plays controversial roles. During in vitro infections, IFN-γ induces the proliferation of the amastigote forms of L. amazonensis. However, this cytokine is not essential at the beginning of an in vivo infection. It is not clear why IFN-γ does not mediate protection during the early stages of infection. Thus, the aim of our study was to investigate the role of IFN-γ during L. amazonensis infection. We infected IFN-γ(-/-) mice in the footpad and followed the development of leishmaniasis in these mice compared with that in WT mice. CD4(+) T lymphocytes and macrophages migrated earlier to the site of infection in the WT mice, and the earlier migration of these 2 cell types was associated with lesion development and parasite growth, respectively. These differences in the infiltrate populations were explained by the increased expression of chemokines in the lesions of the WT mice. Thus, we propose that IFN-γ plays a dual role during L. amazonensis infection; it is an important inducer of effector mechanisms, particularly through inducible nitric oxide synthase expression, and conversely, it is a mediator of inflammation and pathogenesis through the induction of the expression of chemokines. Our data provided evidence for a pathogenic effect of IFN-γ production during leishmaniasis that was previously unknown.
authors.affiliation: 1 Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte, Brazil .
authors.forename: Matheus Batista Heitor
authors.initials: MB
authors.lastname: Carneiro
authors.affiliation: 1 Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte, Brazil .
authors.forename: Mateus Eustáquio de Moura
authors.initials: ME
authors.lastname: Lopes
authors.affiliation: 1 Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte, Brazil .
authors.forename: Leonardo Gomes
authors.initials: LG
authors.lastname: Vaz
authors.affiliation: 1 Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte, Brazil .
authors.forename: Louisa Maria Andrade
authors.initials: LM
authors.lastname: Sousa
authors.affiliation: 1 Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte, Brazil .
authors.forename: Liliane Martins
authors.initials: LM
authors.lastname: dos Santos
authors.affiliation: 2 Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte, Brazil .
authors.forename: Carolina Carvalho
authors.initials: CC
authors.lastname: de Souza
authors.affiliation: 1 Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte, Brazil .
authors.forename: Ana Carolina de Angelis
authors.initials: AC
authors.lastname: Campos
authors.affiliation: 1 Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte, Brazil .
authors.forename: Dawidson Assis
authors.initials: DA
authors.lastname: Gomes
authors.affiliation: 2 Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte, Brazil .
authors.forename: Ricardo
authors.initials: R
authors.lastname: Gonçalves
authors.affiliation: 2 Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte, Brazil .
authors.forename: Wagner Luiz
authors.initials: WL
authors.lastname: Tafuri
authors.affiliation: 1 Departamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais , Belo Horizonte, Brazil .
authors.forename: Leda Quercia
authors.initials: LQ
authors.lastname: Vieira
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D018925:Chemokines / Q000378:metabolism; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006790:Host-Parasite Interactions; D018836:Inflammation Mediators / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D007894:Leishmania mexicana / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000235:genetics / Q000276:immunology* / Q000378:metabolism* / Q000469:parasitology; D008264:Macrophages / Q000276:immunology* / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism
chemical_list: D018925:Chemokines; D016207:Cytokines; D018836:Inflammation Mediators; D007371:Interferon-gamma; D052247:Nitric Oxide Synthase Type II