γδ T cells increase with gastric mucosal interleukin (IL)‐7, IL‐1β, and <i>Helicobacter pylori</i> urease specific immunoglobulin levels via CCR2 upregulation in <i>Helicobacter pylori</i> gastritis

Futagami, Seiji; Hiratsuka, Tetsuro; Suzuki, Kenji; Kusunoki, Masanori; Wada, Ken; Miyake, Kazumasa; Ohashi, Kazushi; Shimizu, Mitsuru; Takahashi, Hidemi; Gudis, Katya; Kato, Shunji; Tsukui, Taku; Sakamoto, Choitsu

doi:10.1111/j.1440-1746.2005.04148.x

Cited by 19 publications

(14 citation statements)

References 33 publications

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“…Smad3 negatively regulates Th17 cell development through FoxP3 (Lu et al, 2010; Tone et al, 2008). In agreement with prior studies (Futagami et al, 2006; Lee et al, 2012; Lundgren et al, 2005), gastric T-reg and Th17 cell response-related genes (e.g., STAT3, Ccr2, Tgfb) were differentially expressed in response to H. pylori (Supplemental File 1). However, we also observed modestly higher levels of Th17 cells and a trend towards more T-reg cells in pulmonary tissues of H. pylori -infected mice, with effects enhanced in the cohort infected at a younger age.…”

Section: Discussionsupporting

confidence: 90%

Gastric Helicobacter pylori Infection Affects Local and Distant Microbial Populations and Host Responses

et al. 2016

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SUMMARY Helicobacter pylori is a late-in-life human pathogen with potential early-life benefits. Although H. pylori is disappearing from the human population, little is known about the influence of H. pylori on the host’s microbiota and immunity. Studying the interactions of H. pylori with murine hosts over six months, we found stable colonization accompanied by gastric histologic and antibody responses. Analysis of gastric and pulmonary tissues revealed increased expression of multiple immune response genes, conserved across mice and over time in the stomach, and more transiently in the lungs. Moreover, H. pylori infection led to significantly different population structures in both the gastric and intestinal microbiota. These studies indicate that H. pylori influences the microbiota and host immune responses not only locally in the stomach, but distantly as well, affecting important target organs.

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Section: Discussionsupporting

confidence: 90%

Gastric Helicobacter pylori Infection Affects Local and Distant Microbial Populations and Host Responses

et al. 2016

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“…In this study, we found that infection with the enteric rodent pathogen C. rodentium promoted IL-7 production from IECs, in agreement with a published study suggesting that H. pylori infection causes increased intestinal IL-7 in humans (32). Therefore, intestinal epithelium-derived IL-7 may be one of the important molecules that inhibit inflammation and infection caused by various bacteria.…”

Section: Discussionsupporting

confidence: 79%

Interleukin-7 Produced by Intestinal Epithelial Cells in Response to Citrobacter rodentium Infection Plays a Major Role in Innate Immunity against This Pathogen

Zhang

Yu³

et al. 2015

Infect Immun

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bInterleukin-7 (IL-7) engages multiple mechanisms to overcome chronic viral infections, but the role of IL-7 in bacterial infections, especially enteric bacterial infections, remains unclear. Here we characterized the previously unexplored role of IL-7 in the innate immune response to the attaching and effacing bacterium Citrobacter rodentium. C. rodentium infection induced IL-7 production from intestinal epithelial cells (IECs). IL-7 production from IECs in response to C. rodentium was dependent on gamma interferon (IFN-␥)-producing NK1.1 ؉ cells and IL-12. Treatment with anti-IL-7R␣ antibody during C. rodentium infection resulted in a higher bacterial burden, enhanced intestinal damage, and greater weight loss and mortality than observed with the control IgG treatment. IEC-produced IL-7 was only essential for protective immunity against C. rodentium during the first 6 days after infection. An impaired bacterial clearance upon IL-7R␣ blockade was associated with a significant decrease in macrophage accumulation and activation in the colon. Moreover, C. rodentium-induced expansion and activation of intestinal CD4 ؉ lymphoid tissue inducer (LTi) cells was completely abrogated by IL-7R␣ blockade. Collectively, these data demonstrate that IL-7 is produced by IECs in response to C. rodentium infection and plays a critical role in the protective immunity against this intestinal attaching and effacing bacterium. Citrobacter rodentium is a mouse extracellular enteric pathogen that mimics human-enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E coli (EHEC). These bacterial pathogens attach intimately to intestinal epithelium and cause subcellular attaching and effacing lesions, which lead to severe diarrhea, vomiting, and fever, with high rates of fatality (1). C. rodentium infection of mice causes epithelial hyperplasia in the colon and cecum, goblet cell loss, and mucosal infiltration with macrophages, lymphocytes, and neutrophils (2). Therefore, this is an ideal model to dissect how immune cells interact with gut epithelial pathogens. The innate immune cells, including macrophages, dendritic cells (DCs), natural killer (NK) cells, neutrophils, and innate lymphoid cells (ILCs) have been shown to play an essential role in the clearance of C. rodentium infection (3-6). Moreover, the adaptive immune cells, mostly T and B cells, are also required for the clearance of this pathogen (7,8). Furthermore, the cytokines interleukin-6 (IL-6), IL-12, IL-17, IL-22, IL-23, and gamma interferon (IFN-␥) are upregulated in the colon tissues of C. rodentium-infected mice and are necessary for an effective immune defense against this pathogen (3-5, 7, 9).IL-7 is a stroma-derived cytokine that can be secreted by fetal liver cells, stromal cells in the bone marrow and thymus, and intestinal epithelial cells (IECs) (10). IL-7 acts on various cells through its receptor, a heterodimer consisting of an alpha-chain (IL-7R␣) and the common cytokine receptor gamma chain. The IL-7 receptor is expressed on lymphoid T and B precursors...

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“…We here evidenced an over production of IL-7 during the first days of acute SIV infection, especially within the small intestine, which may participate to the characteristic cytokine storm occurring during the acute phase of SIV/HIV infection (21). Interestingly, similar enhancements of local IL-7 expression were recently observed in mice infected with C. rodentium , and in humans infected with Helicobacter pylori (23, 43). Earlier and stronger viral infection in the ileum compared to LNs or to other parts of the gut suggests that the presence of infected cells directly triggers local IL-7 production.…”

Section: Discussionsupporting

confidence: 78%

Acute Simian Immunodeficiency Virus Infection Triggers Early and Transient Interleukin-7 Production in the Gut, Leading to Enhanced Local Chemokine Expression and Intestinal Immune Cell Homing

et al. 2017

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The intestinal barrier, one of the first targets of HIV/simian immunodeficiency virus (SIV) is subjected to major physiological changes during acute infection. Having previously shown that pharmaceutical injection of interleukin-7 (IL-7) triggers chemokine expression in many organs leading to massive T-cell homing, in particular to the intestine, we here explored mucosal IL-7 expression as part of the cytokine storm occurring during the acute phase of SIV infection in rhesus macaques. Quantifying both mRNA and protein in tissues, we demonstrated a transient increase of IL-7 expression in the small intestine of SIV-infected rhesus macaques, starting with local detection of the virus by day 3 of infection. We also observed increased transcription levels of several chemokines in the small intestine. In infected macaques, ileal IL-7 expression correlated with the transcription of four of these chemokines. Among these chemokines, the macrophage and/or T-cell attractant chemokines CCL4, CCL25, and CCL28 also demonstrated increased transcription in uninfected IL-7-treated monkeys. Through immunohistofluorescence staining and image analysis, we observed increased CD8+ T-cell numbers and stable CD4+ T-cell counts in the infected lamina propria (LP) during hyperacute infection. Concomitantly, circulating CCR9+beta7+ CD4+ and CD8+ T-cells dropped during acute infection, suggesting augmented intestinal homing of gut-imprinted T-cells. Finally, CD4+ macrophages transiently decreased in the submucosa and concentrated in the LP during the first days of infection. Overall, our study identifies IL-7 as a danger signal in the small intestine of Chinese rhesus macaques in response to acute SIV infection. Through stimulation of local chemokine expressions, this overexpression of IL-7 triggers immune cell recruitment to the gut. These findings suggest a role for IL-7 in the initiation of early mucosal immune responses to SIV and HIV infections. However, IL-7 triggered CD4+ T-cells and macrophages localization at viral replication sites could also participate to viral spread and establishment of viral reservoirs.

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γδ T cells increase with gastric mucosal interleukin (IL)‐7, IL‐1β, and Helicobacter pylori urease specific immunoglobulin levels via CCR2 upregulation in Helicobacter pylori gastritis

Abstract: Gastric mucosal increases in IL-7 and IL-1beta closely corresponded to the accumulation of gammadelta T cells in gastric mucosa. An association was also seen between gammadelta T cell accumulation and H. pylori urease-specific Ig levels.

Cited by 19 publications

References 33 publications

Gastric Helicobacter pylori Infection Affects Local and Distant Microbial Populations and Host Responses

Gastric Helicobacter pylori Infection Affects Local and Distant Microbial Populations and Host Responses

Interleukin-7 Produced by Intestinal Epithelial Cells in Response to Citrobacter rodentium Infection Plays a Major Role in Innate Immunity against This Pathogen

Acute Simian Immunodeficiency Virus Infection Triggers Early and Transient Interleukin-7 Production in the Gut, Leading to Enhanced Local Chemokine Expression and Intestinal Immune Cell Homing

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