Macrophage proliferation, provenance, and plasticity in macroparasite infection

Abstract

Summary:Macrophages have long been center stage in the host response to microbial infection, but only in the past 10–15 years has there been a growing appreciation for their role in helminth infection and the associated type 2 response. Through the actions of the IL-4 receptor α (IL-4Rα), type 2 cytokines result in the accumulation of macrophages with a distinctive activation phenotype. Although our knowledge of IL-4Rα-induced genes is growing rapidly, the specific functions of these macrophages have yet to be established in most disease settings. Understanding the interplay between IL-4Rα-activated macrophages and the other cellular players is confounded by the enormous transcriptional heterogeneity within the macrophage population and by their highly plastic nature. Another level of complexity is added by the new knowledge that tissue macrophages can be derived either from a resident prenatal population or from blood monocyte recruitment and that IL-4 can increase macrophage numbers through proliferative expansion. Here, we review current knowledge on the contribution of macrophages to helminth killing and wound repair, with specific attention paid to distinct cellular origins and plasticity potential.

Local amplifiers of IL-4Rα–mediated macrophage activation promote repair in lung and liver

“…Consistent with the known ability of IL-4 to cause macrophage proliferation during helminth infection (7), aMϕs from WT mice exhibited significant proliferation (Fig. 1M, N) and highly increased aMϕs numbers (Fig.…”

IL-17 and neutrophils: unexpected players in the type 2 immune response

“…smooth muscle, epithelial cells) dictates the outcome of a type 2 immune response. Loss of the IL-4Ra will render experimental animals more susceptible to infection with nematodes highlighting the importance of type 2 immunity for resistance to helminth infection [16][17][18]. The impact of type 2 cytokines is not limited to any particular cell, tissue or body system but a central player is the macrophage, present in virtually all tissues of the body and strongly responsive to IL-4 and IL-13.…”

“…The impact of type 2 cytokines is not limited to any particular cell, tissue or body system but a central player is the macrophage, present in virtually all tissues of the body and strongly responsive to IL-4 and IL-13. IL-4Ra activated macrophages (Mw(IL-4)) have a highly distinctive expression profile in vivo, characterized in mice by the production of the chitinase-like protein Ym1, RELMa and arginase among others [17,19]. Unravelling macrophage function in response to IL-4Ra signalling has opened doors to the enormous spectrum of type 2 immune effector functions [17].…”

Particles from the Echinococcus granulosus laminated layer inhibit IL-4 and growth factor-driven Akt phosphorylation and proliferative responses in macrophages

“…In particular, it drives the activation of macrophages and other myeloid cells in response to IL-4 and IL-13 that is observed at sites of helminth infection1. These IL-4Rα-activated macrophages (M(IL-4)) are characterised by up-regulation of Arginase, resistin-like molecule alpha (Relm-α) and Chitinase like 3 (Chil3/Ym1)123.…”