Intestinal dysbacteriosis induces changes of T lymphocyte subpopulations in Peyer’s patches of mice and orients the immune response towards humoral immunity
© Gao et al.; licensee BioMed Central Ltd. 2012
Received: 9 October 2012
Accepted: 6 December 2012
Published: 11 December 2012
The large numbers of human intestinal microorganisms have a highly co-evolved relationship with the immune system. Dysbacteriosis of intestinal microbiota induces alterations of immune responses, and is closely related to disease development. Peyer’s patches are immune sensors in intestine which exert essential functions during development of inflammatory disease. However, interactions between commensal bacteria and PPs have been poorly characterized. In this study, changes of lymphocyte subpopulations and production of cytokines in PPs of mice with intestinal dysbacteriosis were investigated. The ceftriaxone-induced dysbacteriosis caused a notable change in populations of T lymphocytes, their subpopulations in PPs and expressions of various cytokines. Our results suggest intestinal dysbacteriosis in mice reduces immune tolerance in PPs and orients immune response towards humoral immunity.
Intestinal microorganisms are required for proper development of the immune system, as indicated by the fact that germ-free (GF) mice have poorly developed lymphoid tissues . Under normal conditions, gut microflora exists in a state of equilibrium with host that is mutually beneficial to the degree that it has been described as a separate ‘organ’ adapted to human physiology . However, factors such as antibiotics abuse, stress, or nutritional deficiencies can seriously disrupt this delicate balance, resulting in altered immune responses and disease. In IBD patients, the quantity of commensal bacteria in the intestine is reduced, diversity of microbiota is also altered [3, 4]. Patients with IBD exhibit disruption in mucosal integrity, dysfunction of gut-associated lymphoid tissue (GALT), and deregulated immune tolerance [5, 6]. Nevertheless, whether microbial dysbiosis in the gut is the cause of dysfunction in GALT, and of reduced immune tolerance, are as yet poorly documented. Peyer’s patches (PPs) are major component of GALT. Lacking of PPs and lymph nodes would develop more severe colitis in mice , suggesting PPs’ importance in exerting immune functions during the development of IBD. The participation of PPs in inflammatory disorders and their interplay with gut microbiota is thus becoming an interesting field of research.
Study design and results
The present work describes the effects of intestinal dysbacteriosis on immune responses of PPs in mice. This disturbance in mice can be induced by ceftriaxone sodium, making it an ideal animal model to mimic gut dysbacteriosis in human. Also, this is the first study to document changes in T lymphocyte subpopulations and cytokine mRNA expression of PPs in response to intestinal dysbacteriosis. Dysbacteriosis induced a notable change in overall population of T lymphocytes, and in T lymphocyte subpopulations, in PPs, as well as altering the mRNA expression of various cytokines. These data suggest that immune tolerance in PPs is reduced after the administration of antibiotics, and the immune response has shifted to humoral immunity. However, relevance of these observations requires further study.
This work was supported by grants from National Program on Key Basic Research Project (973 Program, 2013CB531405), and the National Natural Science Foundation of China (NSFC, No.81150014).
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