Pattern of Macrophage Activation in Yersinia‐Resistant and Yersinia‐Susceptible Strains of Mice

Abstract

Th1 cells, in cooperation with activated macrophages, are required to overcome Yersinia enterocolitica infection in mice. The pathway macrophages utilize to metabolize arginine can alter the outcome of inflammation in different ways. The objective of this study was to verify the pattern of macrophages activation in Y. enterocolitica infection of BALB/c (Yersinia‐susceptible) and C57BL/6 (Yersinia‐resistant) mice. Both strains of mice were infected with Y. enterocolitica O:8 WA 2707. Peritoneal macrophages and spleen cells were obtained on the 1st, 3rd and 5th day post‐infection. The iNOS and the arginase activities were assayed in supernatants of macrophage cultures, by measuring their NO/citrulline and ornithine products, respectively. TGFP‐1 production was also assayed. The Th1 and Th2 responses were evaluated in supernatants of lymphocyte cultures, by IFN‐γ and IL‐4 production. Our results showed that in the early phase of Y. enterocolitica infection (1st and 3rd day), the macrophages from C57BL/6 mice produced higher levels of NO/citrulline and lower levels of ornithine than macrophages from BALB/c mice. The infection with Y. enterocolitica leads to an increase in the TGF‐β1 and IL‐4 production by BALB/c mice and to an increase in the IFN‐γ levels produced by C57BL/6 mice. These results suggest that Y. enterocolitica infection leads to the modulation of M1 macrophages in C57Bl/6 mice, and M2 macrophages in BALB/c mice. The predominant macrophage population (M1 or M2) at the 1st and 3rd day of infection thus seems to be important in determining Y. enterocolitica susceptibility or resistance.

Experimental progressive emphysema in BALB/cJ mice as a model for chronic alveolar destruction in humans

“…As a consequence of the Th1 T cell polarization, macrophages from C57BL/6J become classically (M1) activated and produce nitric oxide in response to innate ligands and IFN-␥ (65). This contrasts with the preferential alternative activation (M2 activation) of macrophages by the Th2 cytokine milieu in BALB/cJ mice with the synthesis of arginase 1, RELM␣, and YM1 (54,78). Interestingly, it has been documented that the development of emphysema in cigarette smoke-exposed mice is strain dependent (28,50).…”

Macrophage Polarization in Bacterial Infections

“…Other pathogens stimulate a clear-cut M2 program in macrophages. For instance, Yersinia enterocolitica infection of susceptible BALB/c mice results in arginase-1 activation and TGF␤1 and IL-4 production (54). The M2 reprogramming of macrophages depends on yersinial virulence factors; the infection of murine macrophages with bacteria defective for the Yop-encoded type III secretion system results in M1 polarization (55).…”

The Role of Macrophages and Dendritic Cells in the Initiation of Inflammation in IBD

“…Indeed, down regulation of microbicidal functions in M2 macrophages can render the host more susceptible to certain infections. 22-27 M2 macrophages are also efficient at recruiting Foxp3 + T regulatory (Treg) cells, which would further down regulate local immune responses. 16 Furthermore, unregulated M2 macrophage activity can promote the development of fibrotic lesions through elaboration of TGFβ and enhanced allergic responses.…”