2019
DOI: 10.4049/jimmunol.1701254
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Salmonella enterica Serovar Typhimurium Travels to Mesenteric Lymph Nodes Both with Host Cells and Autonomously

Abstract: Salmonella infection is a globally important cause of gastroenteritis and systemic disease, and is a useful tool to study immune responses in the intestine. Although mechanisms leading to immune responses against Salmonella have been extensively studied, questions remain about how bacteria travel from the intestinal mucosa to the mesenteric lymph nodes (MLN), a key site for antigen presentation. Here, we used a mouse model of infection with Salmonella enterica serovar Typhimurium (STM) to identify changes in i… Show more

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Cited by 47 publications
(48 citation statements)
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“…Dendritic cells and macrophages are responsible for the delivery of S. Typhi from the gut to the liver, and tissue-resident macrophages are presumably the first innate immune cell to interact with S. Typhi after it arrives at the gallbladder [21,22,49,50]. Due to these extensive and early interactions between S. Typhi and macrophages, S. Typhi would be predicted to benefit from the ability to inhibit NO production in vivo.…”
Section: Antigen Has a Direct Effect On Macrophage Nitric Oxide Prmentioning
confidence: 99%
“…Dendritic cells and macrophages are responsible for the delivery of S. Typhi from the gut to the liver, and tissue-resident macrophages are presumably the first innate immune cell to interact with S. Typhi after it arrives at the gallbladder [21,22,49,50]. Due to these extensive and early interactions between S. Typhi and macrophages, S. Typhi would be predicted to benefit from the ability to inhibit NO production in vivo.…”
Section: Antigen Has a Direct Effect On Macrophage Nitric Oxide Prmentioning
confidence: 99%
“…They facilitate S. Tm uptake across the epithelial barrier, [19][20][21] lodge S. Tm within the lamina propria and at systemic sites, 18,22 and act as vessels for S. Tm migration between organs. 23 Consequently, restriction of systemic S. Tm infection may depend on the capacity of both IECs and phagocytes to recognize the pathogen through PRR(s) and mount appropriate counter measures. For an adapted pathogen like S. Tm, this task is complicated by the bacterium's evolved ability to evade PRR recognition, through e.g., context-dependent regulation of its gene expression or inhibition of host-cell signaling.…”
Section: Introductionmentioning
confidence: 99%
“…Altogether, these data demonstrate that i) NAIP/NLRC4 specifically in IECs acts as a firewall against pathogen dissemination from the gut lumen, whereas ii) this inflammasome has minimal impact in phagocyte populations that take up S. Tm in the mucosa, transport the pathogen to the mLN, or lodge the bacteria within this site. 18,19,23 NLRC4, NLRP3 and Caspase-11 inflammasomes are all dispensable during early systemic S. Tm infection As a more direct test for a possible involvement of phagocytes in inflammasome-mediated containment of S. Tm, we employed a systemic infection model. Here, S. Tm (10 4 CFU) were applied intravenously (iv), resulting in a rapid uptake by phagocytes, and subsequent pathogen growth in the spleen and other systemic organs within 6-10 hpi.…”
Section: Introductionmentioning
confidence: 99%
“…We also demonstrate that we can isolate distinct populations of monocytes, macrophages, neutrophils and dendritic cells from the small intestine LP of helminth-infected animals, which had previously been a particular challenge due to the fragile nature of myeloid cells ex-vivo. Together, our data indicate that the isolation protocol that we present here allows the phenotypic and functional The isolation of viable leukocytes from the intestinal LP of naïve mice or those infected with bacterial, viral and protozoan pathogens has been widely published (Bravo-Blas et al, 2019;Cerovic et al, 2013;Goodyear et al, 2014;Isakov et al, 2011;Perona-Wright et al, 2012). In contrast, helminth-infected tissues have been difficult to use as sources of immune cells.…”
Section: Discussionmentioning
confidence: 91%
“…Several protocols exist for the isolation of leukocytes from the small intestine of mice, but the inflamed and mucus-rich conditions of helminth-infected intestines have proven challenging. We set out to optimise isolation conditions for leukocytes from the small intestine LP of mice 14 days post-infection with H.polygyrus, adapting protocols previously used by the Milling group for naïve and bacteriallyinfected tissues (Bravo-Blas et al, 2019;Cerovic et al, 2013). Our previous protocols had resulted in extensive cell death when processing H. polygyrus infected tissues, which we reduced by optimisation of the dissection and digestion workflow and the concentrations of digestion enzymes and EDTA solutions (Figure 1).…”
Section: Resultsmentioning
confidence: 99%