Monocyte and Macrophage-Mediated Pathology and Protective Immunity During Schistosomiasis

Abstract

Infection by Schistosoma parasites culminates in a chronic granulomatous disease characterized by intense tissue fibrosis. Along the course of schistosomiasis, diverse leukocytes are recruited for inflammatory foci. Innate immune cell accumulation in Th2-driven granulomas around Schistosoma eggs is associated with increased collagen deposition, while monocytes and macrophages exert critical roles during this process. Monocytes are recruited to damaged tissues from blood, produce TGF-β and differentiate into monocyte-derived macrophages (MDMs), which become alternatively activated by IL-4/IL-13 signaling via IL-4Rα (AAMs). AAMs are key players of tissue repair and wound healing in response to Schistosoma infection. Alternative activation of macrophages is characterized by the activation of STAT6 that coordinates the transcription of Arg1, Chi3l3, Relma, and Mrc1. In addition to these markers, monocytederived AAMs also express Raldh2 and Pdl2. AAMs produce high levels of IL-10 and TGF-β that minimizes tissue damage caused by Schistosoma egg accumulation in tissues. In this review, we provide support to previous findings about the host response to Schistosoma infection reusing public transcriptome data. Importantly, we discuss the role of monocytes and macrophages with emphasis on the mechanisms of alternative macrophage activation during schistosomiasis.

Lipocalin 2 Is a Regulator During Macrophage Polarization Induced by Soluble Worm Antigens

“…We found that LCN2 may be a positive regulator of macrophage M1 polarization and is closely related to cytokines. Macrophage M1 polarization may reduce liver fibrosis induced by S. japonicum ( Souza et al., 2020 ). Our data revealed that the elevated LCN2 expression in S. japonicum infection might be a positive factor against it by upregulating INOS-mediated activation of macrophage M1.…”

Monocyte dysregulation: consequences for hepatic infections

“…Peripheral monocytes, which are recruited to the site of infection, produce TGF-β and differentiate into monocyte-derived CX 3 CR1 + macrophages, which become alternatively activated due to IL-4/IL-13 signaling via IL-4Rα. This type of macrophage is further characterized by transcription of Arg1, Chi3l3, Relma, and Mrc1 , which is coordinated by STAT6 [ 98 ]. Furthermore, these macrophages are potent producers of pro-fibrinogenic cytokines such as IL-10 and TGF-ß.…”

“…Furthermore, these macrophages are potent producers of pro-fibrinogenic cytokines such as IL-10 and TGF-ß. Interestingly, it seems that recruited Ly6C hi monocytes during schistosomiasis transition directly into alternatively activated macrophages without first adopting the phenotype of Ly6C lo monocytes [ 98 ]. However, Ly6C lo and intermediate Ly6C cells also contribute to pathogenicity; indeed, reduced hepatic accumulation observed in mice with reduced expression of CD18 (ß 2 integrin receptor subunit) results in increased formation of granulomatous lesions in the liver, increased egg deposition, and increased mortality [ 99 ].…”

Trypanosoma evansi evades host innate immunity by releasing extracellular vesicles to activate TLR2-AKT signaling pathway

“…TLRs are expressed by immune cells, like macrophages, dendritic cells (DCs), and neutrophils [ 16 ]. Macrophages resist parasitic infection through phagocytosis, antigen presentation, and activation of other immune cells [ 17 ]. TLRs play a double-edged sword role in parasitic infections.…”