CD18 controls the development and activation of monocyte-to macrophage axis during chronic schistosomiasis
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2022
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Resumo
Schistosomiasis is a neglected tropical disease caused by worms of the genus
Schistosoma spp. The progression of disease results in intense tissue fibrosis
and high mortality rate. After egg deposition by adult worms, the inflammatory
response is characterized by the robust activation of type 2 immunity.
Monocytes and macrophages play critical roles during schistosomiasis.
Inflammatory Ly6Chigh monocytes are recruited from the blood to the
inflammatory foci and differentiate into alternatively activated macrophages
(AAMs), which promote tissue repair. The common chain of b2-integrins (CD18)
regulates monocytopoiesis and mediates resistance to experimental
schistosomiasis. There is still limited knowledge about mechanisms
controlled by CD18 that impact monocyte development and effector cells
such as macrophages during schistosomiasis. Here, we show that CD18low
mice chronically infected with S. mansoni display monocyte progenitors with
reduced proliferative capacity, resulting in the accumulation of the progenitor
cell denominated proliferating-monocyte (pMo). Consequently, inflammatory
Ly6Chigh and patrolling Ly6Clow monocytes are reduced in the bone marrow
and blood. Mechanistically, low CD18 expression decreases Irf8 gene
expression in pMo progenitor cells, whose encoded transcription factor
regulates CSFR1 (CD115) expression on the cell surface. Furthermore, low
CD18 expression affects the accumulation of inflammatory Ly6Chigh CD11b+
monocytes in the liver while the adoptive transference of these cells to
infected-CD18low mice reduced the inflammatory infiltrate and fibrosis in the
liver. Importantly, expression of Il4, Chil3l3 and Arg1 was downregulated,
CD206+PD-L2+ AAMs were reduced and there were lower levels of IL-10 in
the liver of CD18low mice chronically infected with S. mansoni. Overall, these findings suggest that CD18 controls the IRF8-CD115 axis on pMo progenitor
cells, affecting their proliferation and maturation of monocytes. At the same
time, CD18 is crucial for the appropriate polarization and function of AAMs and
tissue repair during chronic schistosomiasis.
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Palavras-chave
b2 integrin, Monocytes, Proliferation, Alternatively activated macrophages, Schistosomiasis
Citação
SOUZA, Camila O. S. et al. CD18 controls the development and activation of monocyte-to-macrophage axis during chronic schistosomiasis. Frontiers in Immunology, Lausanne, v. 13, e929552, 2022. DOI: 10.3389/fimmu.2022.929552. DisponĂvel em: https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.929552/full. Acesso em: 29 jan. 2025.