Abstract
The intestinal commensal microbiota is essential for many host physiological processes, but its impact on infectious diseases is poorly understood. Here we investigate the influence of the gut microbiota during oral Salmonella infection. We report a higher bacterial burden in mesenteric lymph nodes (MLN) of intragastrically infected germ-free (GF) mice compared to conventionally-raised (CONV-R) animals, despite similar inflammatory phagocyte recruitment. Salmonella penetration into the lamina propria of the small intestine and splenic bacterial burden were not altered in the absence of the microbiota. Intragastrically infected GF mice also displayed a higher frequency of IFN-γ-producing NK, NKT, CD4+, and CD8+ T cells in the MLN despite IL-12 levels similar to infected CONV-R mice. However, infecting mice intraperitoneally abrogated the difference in MLN bacterial load and IFN-γ-producing cells observed in intragastrically-infected animals. Moreover, mice treated with antibiotics (ABX) and intragastrically infected with Salmonella had a greater bacterial burden and frequency of IFN-γ-producing cells in the MLN. In ABX mice the number of Salmonella correlated with the frequency of IFN-γ-producing lymphocytes in the MLN, while no such correlation was observed in the MLN of infected GF mice. Overall, the data show that the lack of the microbiota influences pathogen colonization of the MLN, and the increased IFN-γ in the MLN of infected GF mice is not only due to the absence of commensals at the time of infection but the lack of immune signals provided by the microbiota from birth.
Highlights
90% of the cells in the human body are microbes that reside in environmentally exposed surfaces (Cani and Delzenne, 2011)
GF and CONV-R mice were intragastrically infected with S. typhimurium and the bacterial load in Peyer’s patches (PP), small intestine lamina propria (siLP), mesenteric lymph nodes (MLN), and spleen were determined at days 3 and 6 post infection (p.i.)
Similar to the results with GF mice, higher CFUs were found in MLN, but not in PP, siLP, or spleen of ABX mice compared to controls at day 6 p.i. (Figure 1C)
Summary
90% of the cells in the human body are microbes that reside in environmentally exposed surfaces (Cani and Delzenne, 2011). The Intestinal Microbiota and Oral Salmonella Infection metabolic functions (Tremaroli and Bäckhed, 2012; Karlsson et al, 2013; Wichmann et al, 2013), stimulating the intestinal and systemic immune compartments (Talham et al, 1999; Mazmanian et al, 2005) and maintaining mucosal homeostasis (Atarashi et al, 2008; Ivanov et al, 2009; Maynard et al, 2012) In addition to these commensal influences on homeostasis, they play a protective role against invading pathogens. Ways that Salmonella subverts competition with commensals include producing energy more efficiently using products of reactive oxygen species released as a result of inflammation (Winter et al, 2010) Another example is the ability of Salmonella to acquire the essential metal zinc, despite zinc sequestration by calprotectin produced by neutrophils recruited during infection, through a high affinity zinc transporter (Liu et al, 2012). Recolonizing germ-free mice (GF) with species-specific microbiota restored the intestinal immune compartment and reduced Salmonella fecal CFUs 4 days post infection (Chung et al, 2012)
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