Increased susceptibility to primary infection with Listeria monocytogenes in germfree mice may be due to lack of accumulation of L-selectin+ CD44+ T cells in sites of inflammation

Abstract

The host defense of germfree (GF) mice against primary infection with Listeria monocytogenes was compared with that of specific-pathogen-free (SPF) mice. In SPF mice, the numbers of bacteria in the peritoneal cavity, liver, and spleen decreased gradually to undetectable levels by day 8 after intraperitoneal infection with a sublethal dose (2 ؋ 10 3 CFU) of L. monocytogenes. On the other hand, the elimination of bacteria in these organs of GF mice was significantly impaired at this stage after inoculation. We have reported previously that T cells coexpressing L-selectin and CD44 play an important role in protection against L. monocytogenes through trafficking to sites of inflammation. Consistent with our previous findings, the number of unique L-selectin ؉ CD44 ؉ T cells in the peritoneal cavity was remarkably increased on day 8 after infection in SPF mice, whereas such an increase was not evident in GF mice at this stage. Listeria-specific T-cell proliferation was normally detected in the lymph node cells of GF mice inoculated with L. monocytogenes, whereas the T-cell-proliferative response of the peritoneal exudate cells of GF mice was significantly impaired compared with that of SPF mice. These results suggest that the priming of T cells against listerial antigens normally occurs in the peripheral lymphoid organs of GF mice but the trafficking of the activated T cells to the inflamed sites may be severely impaired in GF mice, resulting in increased susceptibility to infection with L. monocytogenes.

Lack of microbiota reduces innate responses and enhances adaptive immunity againstListeria monocytogenesinfection

“…However, the induction of pathogen-specific primary and secondary CD4 + and CD8 + T-cell responses in intestinal and nonintestinal tissues of GF mice has not yet been analyzed. High susceptibility of GF mice to infection with L. monocytogenes has previously been attributed to impaired homing of T lymphocytes at the site of inflammation [9]. Our results suggest that lack of microbiota primarily impairs early recruitment and activation of granulocytes.…”

Microbiota signalling through MyD88 is necessary for a systemic neutrophilic inflammatory response

“…Mice bred in germ-free conditions are more susceptible to pathogens like Salmonella enterica, 4 Listeria monocytogenes, 5 Klebsiella pneumonia 6 and Candida albicans. 7 The role of intestinal flora in preventing enteric infections was initially attributed to its ability to prevent invasion and colonization by opportunist pathogens in the intestinal niche.…”

Listeria monocytogenes in laboratory mice: a model of short‐term infectious and pathogenic processes controllable by regulated protective immune responses

“…Chemokines and adhesion molecules are critical to the circulatory and migratory properties of leukocytes (74,75), which contribute to the efficient surveillance of tissues through their regulated accumulation within the extravascular compartments (28,30,76). The expression of adhesion molecules is precisely and finely regulated according to leukocyte and endothelial cell types, functional state, anatomical localization and the nature of the endothelium-and extracellular matrix-associated chemokines (75,76). L. monocytogenes within blood-fiitering tissues: the transient infectious processes driven in the spleen and liver and their connection with immune system reactivity Following intravenous inoculation, L. monocytogenes is first found predominantly in those tissues containing large numbers of resident mononuclear phagocytes and known to act as filters of bloodborne pathogens, i.e.…”