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.

DOI: 10.1089/jir.2015.0043

Cite this paper

@article{Carneiro2015IFNDependentRO, title={IFN-γ-Dependent Recruitment of CD4(+) T Cells and Macrophages Contributes to Pathogenesis During Leishmania amazonensis Infection.}, author={Matheus Batista Heitor Carneiro and Mateus Eust{\'a}quio de Moura Lopes and Leonardo Gomes Vaz and Louisa Maria Andrade Sousa and Liliane Martins dos Santos and Carolina Carvalho de Souza and Ana Carolina de Angelis Campos and Dawidson Assis Gomes and Ricardo Gonçalves and Wagner Luiz Tafuri and Leda Quercia Vieira}, journal={Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research}, year={2015}, volume={35 12}, pages={935-47} }