M.neoaurum infection increased the inhibitory function of Tregs and the death rate associated with Salmonella coinfection

Abstract

Mycobacterium neoaurum belongs to the nontuberculous mycobacteria (NTM) and is ubiquitously present in the environment. However, the changes in Treg percentages and suppressive properties in mice infected with M. neoaurum are still not elucidated. In this study, mice were intraperitoneally injected with M. neoaurum. The change in the CD4⁺CD25⁺ Treg cell percentage in the spleen was analyzed using flow cytometry. There was a significant increase in the number of CD4⁺CD25⁺ cells by week 6 postinfection, with a peak proportion of approximately 2%. The Foxp3 and IL-10 mRNA expression in CD4⁺CD25⁺ cells from the spleens of M.neoaurum-infected mice was higher than that in CD4⁺CD25⁺ cells from the spleens of noninfected controls. Proliferation suppression assay results indicated that CD4⁺CD25⁺ cells suppressed the proliferation of CD4⁺CD25^- cells at week 6 after M.neoaurum infection, and the suppression rate reached 89.8%. However, CD4⁺CD25⁺ cells from the noninfected control group did not suppress the proliferation of CD4⁺CD25^- cells. Based on the above results, mice were subjected to oral administration of S. Typhimurium at 6 weeks postinfection with M. neoaurum, and we found that the mortality of the M.neoaurum-S. Typhimurium infection group was higher than that of the S. Typhimurium infection group. In addition, serious pathological changes appeared in the liver and cecum of the M.neoaurum-S.Typhimurium infection group compared with those of the S. Typhimurium infection group. M. neoaurum increased Treg percentages and suppressed spleen function in mice. These results revealed the possibility that persistent M.neoaurum infection could increase the occurrence of secondary infection.

Keywords: Infection; Mycobacterium neoaurum; Proliferation; S. Typhimurium; Treg cell.