Macrophages and neutrophils cooperate in immune responses to Leishmania infection.

Neutrophils and macrophages are phagocytic cells that cooperate during inflammation and tissue repair. Neutrophils undergo apoptosis and are engulfed by macrophages. Engulfment modulates macrophage activation and microbicidal activity. Infection by Leishmania takes place in the context of tissue repair. This article discusses cellular and molecular mechanisms involved in the intimate cooperation of neutrophils and macrophages in Leishmania infection.

Proinflammatory clearance of apoptotic neutrophils induces an IL-12(low)IL-10(high) regulatory phenotype in macrophages.

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.