Ly6Chi Monocyte Recruitment Is Responsible for Th2 Associated Host-Protective Macrophage Accumulation in Liver Inflammation due to Schistosomiasis

Abstract

Accumulation of M2 macrophages in the liver, within the context of a strong Th2 response, is a hallmark of infection with the parasitic helminth, Schistosoma mansoni, but the origin of these cells is unclear. To explore this, we examined the relatedness of macrophages to monocytes in this setting. Our data show that both monocyte-derived and resident macrophages are engaged in the response to infection. Infection caused CCR2-dependent increases in numbers of Ly6Chi monocytes in blood and liver and of CX3CR1+ macrophages in diseased liver. Ly6Chi monocytes recovered from liver had the potential to differentiate into macrophages when cultured with M-CSF. Using pulse chase BrdU labeling, we found that most hepatic macrophages in infected mice arose from monocytes. Consistent with this, deletion of monocytes led to the loss of a subpopulation of hepatic CD11chi macrophages that was present in infected but not naïve mice. This was accompanied by a reduction in the size of egg-associated granulomas and significantly exacerbated disease. In addition to the involvement of monocytes and monocyte-derived macrophages in hepatic inflammation due to infection, we observed increased incorporation of BrdU and expression of Ki67 and MHC II in resident macrophages, indicating that these cells are participating in the response. Expression of both M2 and M1 marker genes was increased in liver from infected vs. naive mice. The M2 fingerprint in the liver was not accounted for by a single cell type, but rather reflected expression of M2 genes by various cells including macrophages, neutrophils, eosinophils and monocytes. Our data point to monocyte recruitment as the dominant process for increasing macrophage cell numbers in the liver during schistosomiasis.

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

“…Again similar to resident macrophages, the proliferation caused by IL-4c was also observable in the pleural cavity (Figure S4), reaching significance for MHCII high macrophages (Figure S4C). We also analysed F4/80 low MHCII high CD11c + cells, a gate previously considered as corresponding to DCs only, but now recognised to additionally contain bone marrow-derived macrophages734. We will refer to cells in this gate as CD11c + antigen-presenting cells (APC) (Figure S2).…”

“…Macrophages proliferate locally in diverse models of immunological granuloma4142434445 and in the local reaction against several different tissue-dwelling helminths157. Macrophage-rich, granulomatous reactions are associated with poor survival/vitality of Echinococcus larvae, but these reactions do not develop in most host species/contexts15161718192324.…”

“…In others (e.g. Schistosoma mansoni ) monocyte recruitment makes the dominant contribution to macrophage numbers but proliferation of macrophages still occurs167. Proliferation is also essential in homeostatic maintenance of the numbers of resident macrophages in many tissues, typically driven by the growth factor M-CSF89.…”

CX3CL1–CX3CR1 Interaction Increases the Population of Ly6C−CX3CR1hi Macrophages Contributing to Unilateral Ureteral Obstruction–Induced Fibrosis

“…In addition, the CCR2/CX3CR1 receptor switch promoted macrophages adhere to coronary artery smooth muscle cells and accumulate in vessel wall (30). In kidney ischemia-reperfusion injury, CCR2 and CX3CR1 mediate monocyte/macrophage migration into inflamed tissue (11) and CCR2 2/2 mice are protected from Schistosomiasis infection owing to an attenuation of monocyte egress from bone marrow (31). Our studies compliment these results and demonstrate a causal relation between CCR2-expressing monocytes/macrophages and tissue injury following renal obstruction.…”

SjE16.7 activates macrophages and promotes Schistosoma japonicum egg-induced granuloma development

“…Data was acquired using an Olympus DP12 digital camera controlled by CellSens Standard software. Slides were read and interpreted in a blinded fashion and the diameters of granulomas (around single eggs) were measured (Nascimento et al, 2014;Smith et al, 2005).…”