The CXC Chemokine Murine Monokine Induced by IFN-γ (CXC Chemokine Ligand 9) Is Made by APCs, Targets Lymphocytes Including Activated B Cells, and Supports Antibody Responses to a Bacterial Pathogen In Vivo

Abstract

Monokine induced by IFN-γ (Mig; CXC chemokine ligand 9) is an IFN-γ-inducible CXC chemokine that signals through the receptor CXCR3 and is known to function as a chemotactic factor for human T cells, particularly following T cell activation. The mig gene can be induced in multiple cell types and organs, and Mig has been shown to contribute to T cell infiltration into immune/inflammatory reactions in peripheral tissues in mice. We have investigated the expression and activities of Mig and CXCR3 in mouse cells and the role of Mig in models of host defense in mice. Murine (Mu)Mig functioned as a chemotactic factor for resting memory and activated T cells, both CD4+ and CD8+, and responsiveness to MuMig correlated with surface expression of MuCXCR3. Using mig−/− mice, we found that MuMig was not necessary for survival after infections with a number of intracellular pathogens. Surprisingly, however, we found that mig−/− mice showed reductions of 50–75% in Abs produced against the intracellular bacterium Francisella tularensis live vaccine strain. Furthermore, we found that MuMig induced both calcium signals and chemotaxis in activated B cells, and that B cell activation induced expression of MuCXCR3. In addition, IFN-γ induced the expression of mumig in APCs, including CD8α+ and CD8α− dendritic cells. Together, our data suggest that Mig and CXCR3 may be important not only to recruit T cells to peripheral inflammatory sites, but also in some cases to maximize interactions among activated T cells, B cells, and dendritic cells within lymphoid organs to provide optimal humoral responses to pathogens.

Identification of the Molecular Mechanism by which TLR Ligation and IFN‐γ Synergize to Induce Mig

“…In addition, this group has shown that IFN-g can induce MIG in dendritic cells (Park et al, 2002). Taken together, these data implicate MIG as playing a key role in the adaptive immune response by recruiting T cells and enhancing their interactions with B cells and dendritic cells (Park et al, 2002).…”

“…It is also involved in the pathogenesis of a number of autoimmune disorders as well as the development of atherosclerosis (Liu et al, 2001;Belperio et al, 2002;Mahad et al, 2002;Yun et al, 2002). Recently, by examining MIG null mice, Park et al, have revealed a role for MIG in skewing toward a TH1 immune response as well as contributing to the optimal generation of humoral immune responses to intracellular bacterial infections (Park et al, 2002). In addition, this group has shown that IFN-g can induce MIG in dendritic cells (Park et al, 2002).…”

“…Recently, by examining MIG null mice, Park et al, have revealed a role for MIG in skewing toward a TH1 immune response as well as contributing to the optimal generation of humoral immune responses to intracellular bacterial infections (Park et al, 2002). In addition, this group has shown that IFN-g can induce MIG in dendritic cells (Park et al, 2002). Taken together, these data implicate MIG as playing a key role in the adaptive immune response by recruiting T cells and enhancing their interactions with B cells and dendritic cells (Park et al, 2002).…”

CD4+ T cell migration into the cornea is reduced in CXCL9 deficient but not CXCL10 deficient mice following herpes simplex virus type 1 infection

“…Wild type (WT) male and female C57BL/6 (The Jackson Laboratory, Bar Harbor, ME), CXCL9−/− [44], and CXCL10−/− [22] mice (6-12 weeks of age) were housed in sterile cages under pathogen free conditions. CXCL9−/− mice were backcrossed onto a C57BL/6 background 8 generations and CXCL10−/− mice were backcrossed 9 generations.…”

Oligomerization of Vibrio Cholerae Hemolysin Induces CXCR3 Upregulation and Activation of B-1a Cell

“…However, the CXCR3 ligands CXCL9 and CXCL10 can also induce increased survival and growth of mesangial cells through the same receptor (13). Since the expression of CXCR3 could be traced only on activated murine B cells (14) as opposed to normal and malignant B cells in humans (7), it becomes essential to ascertain its involvement in the HlyA oligomer mediated activation of B-1a cells.…”