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Alessandra A Filardy, Dayana R Pires, Marise P Nunes, Christina M Takiya, Celio G Freire-de-Lima, Flavia L Ribeiro-Gomes, George A DosReis, Proinflammatory Clearance of Apoptotic Neutrophils Induces an IL-12lowIL-10high Regulatory Phenotype in Macrophages, The Journal of Immunology, Volume 185, Issue 4, August 2010, Pages 2044–2050, https://doi.org/10.4049/jimmunol.1000017
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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.