Chemokines at mucosal barriers and their impact on HIV infection

Rancez, Magali; Couëdel-Courteille, Anne; Cheynier, Rémi

doi:10.1016/j.cytogfr.2012.05.010

Cited by 17 publications

(22 citation statements)

References 161 publications

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“…In both steady-state and inflammatory conditions, immune cell homing to and within the intestinal mucosa is regulated by various homeostatic or inflammatory chemokines (24). CCL20 and CCL25, which are produced by epithelial cells in the small intestine, respectively, participate in the steady-state maintenance of CCR6 + and CCR9 + lymphocyte traffic into organized lymphoid structures (25–27).…”

Section: Introductionmentioning

confidence: 99%

“…CCL19 and CCL21, which are expressed by endothelial and stromal cells, attract CCR7 + cells into lymphoid aggregates. CXCL12 participates in the localization of plasma cells and T-cells into both the follicles and into the LP (24, 29). During an inflammatory response, immune cell homing to the gut requires CCL2, CCL3, CCL4, and CCL5, as well as CXCL10, which are mostly expressed by epithelial cells (24).…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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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“…Most of the mucosal surfaces of the respiratory, GI, and urogenital tracts are lined by an epithelial barrier that provides non-specific and innate defenses including mucins and antimicrobial proteins. Epithelial cells detect dangerous foreign components through pattern-recognition receptors such as Toll-like receptors (TLRs), sending cytokine and chemokine signals to underlying mucosal cells including dendritic cells (DCs) and macrophages [6,7]. These trigger innate nonspecific defenses and together with intraepithelial lymphocytes and cells in the lamina propria, promote adaptive immune responses against pathogens such as HIV [8].…”

Section: Evaluating Mucosal Immunitymentioning

confidence: 99%

Challenges in Mucosal HIV Vaccine Development: Lessons from Non-Human Primate Models

Tuero

Robert-Guroff

2014

Viruses

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An efficacious HIV vaccine is urgently needed to curb the AIDS pandemic. The modest protection elicited in the phase III clinical vaccine trial in Thailand provided hope that this goal might be achieved. However, new approaches are necessary for further advances. As HIV is transmitted primarily across mucosal surfaces, development of immunity at these sites is critical, but few clinical vaccine trials have targeted these sites or assessed vaccine-elicited mucosal immune responses. Pre-clinical studies in non-human primate models have facilitated progress in mucosal vaccine development by evaluating candidate vaccine approaches, developing methodologies for collecting and assessing mucosal samples, and providing clues to immune correlates of protective immunity for further investigation. In this review we have focused on non-human primate studies which have provided important information for future design of vaccine strategies, targeting of mucosal inductive sites, and assessment of mucosal immunity. Knowledge gained in these studies will inform mucosal vaccine design and evaluation in human clinical trials.

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“…Lymphoid cells can be orchestrated by chemokines, trafficking and positioning into different mucosa-associated lymphoid tissues, contributing to immune defence (Rancez et al, 2012). Prebiotics therefore have the potential to modulate lymphoid cells and stimulate the gut immune system (Forchielli and Walker, 2005;Daddaoua et al, 2007;Geraylou et al, 2012).…”

Section: Prebiotics and The Gut Immune Systemmentioning

confidence: 99%

“…The gut mucosal lining contains organized lymphoid tissues that support the initiation of antimicrobial immune responses (Rancez et al, 2012). Lymphoid cells can be orchestrated by chemokines, trafficking and positioning into different mucosa-associated lymphoid tissues, contributing to immune defence (Rancez et al, 2012).…”

Section: Prebiotics and The Gut Immune Systemmentioning

confidence: 99%

Prebiotics: A Potential Treatment Strategy for the Chemotherapy-damaged Gut?

Wang

Geier

Howarth

2014

Critical Reviews in Food Science and Nutrition

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Mucositis, characterized by ulcerative lesions along the alimentary tract, is a common consequence of many chemotherapy regimens. Chemotherapy negatively disrupts the intestinal microbiota, resulting in increased numbers of potentially pathogenic bacteria, such as Clostridia and Enterobacteriaceae, and decreased numbers of "beneficial" bacteria, such as Lactobacilli and Bifidobacteria. Agents capable of restoring homeostasis in the bowel microbiota could therefore be applicable to mucositis. Prebiotics are indigestible compounds, commonly oligosaccharides, which seek to reverse chemotherapy-induced intestinal dysbiosis through selective colonization of the intestinal microbiota by probiotic bacteria. In addition, evidence is emerging that certain prebiotics contribute to nutrient digestibility and absorption, modulate intestinal barrier function through effects on mucin expression, and also modify mucosal immune responses, possibly via inflammasome-mediated processes. This review examines the known mechanisms of prebiotic action and explores their potential to reduce the severity of chemotherapy-induced mucositis in the intestine. MUCOSITISThe treatment of cancer by chemotherapy, sometimes in combination with radiotherapy, is associated with an array of acute side-effects, including alopecia, neutropenia and nausea (Logan et al., 2007). Furthermore, these treatments can also induce inflammation and deterioration of the mucosal membranes of the alimentary tract, a condition referred to as mucositis. Mucositis can occur throughout the entire gastrointestinal tract (Gibson et al., 2005); however, it most commonly affects the mucosa of the mouth (oral mucositis) and small intestine (gastrointestinal mucositis), with symptoms including pain, vomiting, bloating, and diarrhoea. Severe cases are often associated with secondary complications such as malnutrition and septicaemia, resulting in poor patient outcomes. Indeed, the pathobiology of mucositis is influenced by the nature of the causative agent (Logan et al., 2009), with temporal variations in pathogenesis, in addition to the location and severity of damage (Logan et al., 2009). Consequently, the multi-factorial nature of mucositis makes it a difficult condition to understand, and subsequently treat.Despite mucositis being one of the most common side-effects of cancer treatment (Choi et al., 2007) its incidence and severity is highly variable, and is dependent on the treatment regimen and individual variation in terms of tolerability . Approximately 40% of all patients undergoing chemotherapy develop mucositis (Gibson et al., 2002; with this number rising to between 60% and 100% in patients receiving high-dose chemotherapy regimens for conditions such as the haematological malignancies (Gibson et al., 2002;. To date, effective treatments for intestinal mucositis have been elusive. Potential treatment options are limited by the requirement for treatments to protect the mucosa and promote the repair process, without compromising cytotoxic effects on the ...

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Chemokines at mucosal barriers and their impact on HIV infection

Cited by 17 publications

References 161 publications

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

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

Challenges in Mucosal HIV Vaccine Development: Lessons from Non-Human Primate Models

Prebiotics: A Potential Treatment Strategy for the Chemotherapy-damaged Gut?

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