Role of interplay between IL-4 and IFN-γ in the in regulating M1 macrophage polarization induced by Nattectin

Abstract

Recently our group described that Nattectin, a C-type lectin of the venom of Thalassophryne nattereri shows a potent pro-inflammatory capacity. Here, we demonstrated that Nattectin is able to induce M1 macrophage marker iNOS, and up-regulate the expression of MHC class II, CD80, CD86 and CD40 molecules. The increase in MHC class II and CD49a integrin expression with MMP-9 production and endocytic capacity depend on lectin function of Nattectin. Moreover, the polarization of peritoneal and bone marrow-derived macrophages induced by Nattectin to M1 profile is dependent on Th1 cytokines (IL-12 and IFN-γ), and negatively regulated by Th2 cytokines (IL-4, IL-10 and IL-13). Also we reveal that IL-4 play a dual role in this polarization: a regular action of IL-4 was seen in the negative regulation of the CD40 expression, but an unexpected positive regulation was seen in the expression of CCR7 and MHC class II. Finally, our in vivo studies showed that the influx of neutrophils and small peritoneal macrophage--F4/80(low)MHCII(hi) induced by Nattectin is totally dependent on IL-4 and IFN-γ cytokines. Furthermore, the induction of IL-6 release is negatively regulated by IL-4 and positively regulated by IL-12 and IFN-γ. Together, the results allowed us to expand the knowledge about the regulation of macrophage activation, as well as confirmed the ability of Nattectin, a fish C-type lectin, as an important immunomodulatory agent.

Reduction of eotaxin production and eosinophil recruitment by pulmonary autologous macrophage transfer in a cockroach allergen-induced asthma model

“…These data show that CRA exposure has a significant effect on the lung macrophage population, as assessed by their surface expression levels of CD80 and CD86. Studies by other groups using these molecules as M1 markers (19,35,39) suggest that our observations represent genuine phenotypic changes. This provides evidence suggesting a role for macrophage phenotypes in the pathogenesis seen in our model.…”

“…In this study, we have shown that exposure to CRA has a significant effect on macrophage phenotypes, increasing the number of macrophages in the lung and reducing their surface expression of CD80 and CD86, molecules, which, among others, have been previously established as useful in assessing the phenotype of macrophages (1,10,19,20,35,39,51). We have also developed a novel procedure to supplement the lung macrophage population in our outbred mouse model; to our knowledge the use of an ATM has never been investigated in the CRA-induced asthma model.…”

“…Several studies in both mice (19,35) and humans (1,20) have shown an association between reduction of CD80 and CD86 and the reduction of M1 characteristics. Additional studies have shown the association of low expression levels of CD80 and CD86 with the M2 phenotype (10,39,51).…”

“…These two molecules have important roles in the generation of adaptive immune responses (31,57), but in this study their expression levels were assessed as markers of phenotypic change. In conjunction with well-established markers of the M2 phenotype such as Ym1 and Fizz1 (40), reduction in expression levels of CD80 and CD86 has been previously used in other studies as a marker of a reduction in M1 macrophage characteristics (19,35,39).…”

TNF-alpha modulates adipose macrophage polarization to M1 phenotype in response to scorpion venom

“…& Fatima Laraba-Djebari flaraba@hotmail.com; flaraba@usthb.dz fish venom, was able to induce macrophage activation and upregulate the expression of NOS 2 [10]. In addition, the toxic components from Tityus serrulatus (TSV) venom stimulated the release of NO in the presence of LPS in the murine macrophage cell line [11].…”