Vanin‐1 controls granuloma formation and macrophage polarization in Coxiella burnetii infection

Abstract

Q fever is caused by Coxiella burnetii, a bacterium that survives in MU. Vanin-1 is a membrane-anchored pantetheinase that controls tissue inflammation. Consequently, Vanin-1-deficient mice represent a unique mouse model in which stress-induced inflammation is limited by the reaction of resident tissue cells. To investigate the contribution of host tissues in the control of a bacterial infection, we infected Vanin-1-deficient mice with C. burnetii. Mortality and morbidity of mice were not affected. The lack of Vanin-1 had no effect on C. burnetii clearance but decreased the formation of granulomas in spleen and liver. Granuloma formation depends upon MU recruitment and activation in these tissues. Whereas the former was slightly impaired in mutant mice, the lack of Vanin-1 significantly affected the activation pattern of BM-derived MU stimulated by C. burnetii. While their microbicidal activity against C. burnetii was moderately impaired, they exhibited decreased inducible nitric oxide synthase (iNOS) and MCP-1 gene expression, and increased IL-10 and arginase expression. In liver from mutant mice, increased arginase expression and decreased expression of MCP-1 and iNOS were reminiscent of MU data. These results suggest a role of Vanin-1 in granuloma formation in response to C. burnetii by skewing MU activation toward an M2 program. See accompanying commentary http://dx

From phagocyte diversity and activation to probiotics: Back to Metchnikoff

“…In vivo counterparts of M2 macrophage polarization have been observed in tissue remodelling during ontogenesis [28], chronic inflammation [29][30][31][32][33][34][35][36][37][38][39][40][41][42], cancer [9,12,16,17], bacterial [43][44][45][46][47][48][49] and parasitic [50][51][52][53] infections. Evidence has also accumulated that polarized macrophages are more than mere spectators of immunopathology [35][36][37][38][39][40][41][50][51][52].…”

“…The issue of lineage of the actual effectors of MDSC-mediated suppression is even more relevant when their recruitment and activation in non-lymphoid tissues is considered. For instance, do MDSC retain an immature phenotype in tumour tissues or do they differentiate into tumourassociated macrophages [9][10][11] [9,12,16,17], bacterial [43][44][45][46][47][48][49] and parasitic [50][51][52][53] infections. Evidence has also accumulated that polarized macrophages are more than mere spectators of immunopathology [35][36][37][38][39][40][41][50][51][52].…”

New vistas on macrophage differentiation and activation

“…In the study by Helming and Gordon [6] in this issue of the Journal, the authors take advantage of a tagging strategy to determine that MGC formation is a multistep process associated with IL-4-driven alternative (M2) macrophage activation. The approach described in this study [6] is likely to pave the way to the identification of the pathways involved in and the function of MGC formation.In response to cytokines and microbial products, mononuclear phagocytes express specialized and polarized functional properties [1][2][3][4]. Mirroring the Th1/Th2 nomenclature, many refer to polarized macrophages as M1 and M2 cells.…”

“…Evidence published in this issue of the European Journal of Immunology, together with other recent data, add new elements and perspectives to the current understanding of mononuclear phagocyte differentiation and activation and are discussed in this Commentary. Heterogeneity and plasticity are hallmarks of cells belonging to the monocyte-macrophage lineage [1][2][3][4]. Lineage-defined populations of mononuclear phagocytes have not been identified, but already by the shortlived stage of circulating precursor monocytes subsets characterized by the differential expression of the FccRIII receptor (CD16) or of chemokine receptors (CCR2, CX3CR1 and CCR8) and by different functional properties have been described.…”

La polarisation des macrophages, le noeud gordien des infections bactériennes ?

“…La réponse à C. burnetii des macrophages qui surexpriment l'IL-10 est clairement de type M2 [28]. Ces résultats sont à rapprocher de ceux observés dans un autre modèle d'infection persistante à C. burnetii : les souris déficientes en vanine-1, une pantéthéinase ancrée dans la membrane qui contrôle l'inflammation tissulaire, présentent également un profil M2 de leurs macrophages [29]. Nous avons montré récemment que l'ingestion de cellules apoptotiques par les monocytes et les macrophages est critique pour l'évolution chronique de la fièvre Q.…”