CD18 regulates monocyte-macrophage DC progenitors and the differentiation into alternatively activated macrophages during schistosomiasis

Abstract

Abstract Infection with Schistosoma mansoni causes a chronic parasitic disease. Along the course of schistosomiasis, innate immune cells are recruited and accumulate into Th2-granuloma in the liver. Recently, our group demonstrated that the common chain of β2-integrin (CD18) was crucial for monocytopoiesis and resistance to experimental S. mansoni infection. Inside the tissue, inflammatory monocytes (IMs) differentiate and polarize in alternatively activated macrophages (AAMs) in a type 2 microenvironment. In this context, we evaluated the role of CD18 on monocytes progenitors and differentiation into AAMs during chronic schistosomiasis. First, we evaluated the monocyte progenitor cells in the bone marrow from wild-type (WT) and CD18low mice. The low expression of CD18 increased the frequency and absolute number of monocyte-macrophage DC progenitor (MDP), while MFI of Ki-67 were reduced on MDP and common monocytes progenitor (cMoP) at 7 weeks post infection (wpi). Next, we evaluated the integrins family in the liver from S. mansoni-infected mice. We showed increase expression of Itgam when compared to Itgal in the liver at 7 wpi. The frequency of CD11b+cells also increased at 7 wpi, compared to CD11a+ cells. Moreover, compared to WT mice, CD18low animals reduced the MFI of CD11b and CD11c in IMs. The alternative activation markers, Chil3l3 and Arg1 were reduced in CD18low. Indeed, compared to WT mice, CD18low animals reduced the percentage of CD206+PD-L2+ AAMs in the liver at 7 wpi. In addition, the adoptive transference of IMs to CD18low mice reduces the inflammatory infiltrate in the liver at 7 wpi. Overall, our data indicate CD18 coordinated the monocytes differentiation into AAMs during chronic S. mansoni infection.