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Proinflammatory Clearance of Apoptotic Neutrophils Induces an IL-12lowIL-10high Regulatory Phenotype in Macrophages

2010; American Association of Immunologists; Volume: 185; Issue: 4 Linguagem: Inglês

10.4049/jimmunol.1000017

1550-6606

Alessandra A. Filardy, Dayana R. Pires, Marise P. Nunes, Christina Maeda Takiya, Célio Geraldo Freire-de-Lima, Flávia Lima Ribeiro-Gomes, George A. DosReis,

Immune responses and vaccinations

Abstract Clearance of apoptotic exudate neutrophils (efferocytosis) induces either pro- or anti-inflammatory responses in mouse macrophages depending on host genetic background. In this study, we investigated whether neutrophil efferocytosis induces a stable macrophage phenotype that could be recalled by late restimulation with LPS. Bone marrow-derived macrophages previously stimulated by pro- but not anti-inflammatory neutrophil efferocytosis expressed a regulatory/M2b phenotype characterized by low IL-12 and high IL-10 production following restimulation, increased expression of LIGHT/TNF superfamily 14, Th2-biased T cell responses, and permissive replication of Leishmania major. Induction of regulatory/M2b macrophages required neutrophil elastase activity and was partially dependent on TLR4 signaling. These results suggested that macrophage differentiation to a regulatory phenotype plays a role in resolution of inflammation but could contribute to increased humoral Ab responses and parasite persistence in the infected host.