CCR9+ T cells contribute to the resolution of the inflammatory response in a mouse model of intestinal amoebiasis

Rojas-López, A.E.; Soldevila, Gloria; Meza-Pérez, Selene; Dupont, Guillaume; Ostoa‐Saloma, Pedro; Wurbel, Marc‐André; Ventura‐Juárez, Javier; Flores‐Romo, Leopoldo; García‐Zepeda, Eduardo A.

doi:10.1016/j.imbio.2012.04.005

Cited by 12 publications

(8 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, we found that IL-10 is significantly reduced (more than 60%) in CCR9 KO compared to WT mice ( Figure 3 ). These results indicate that, unlike previous data reported in the gut mucosa, where the absence of CCR9 results in increased inflammation [ 17 ], during an allergic inflammatory process in the lung, CCR9 expression correlates with increased leukocyte recruitment, despite the reduced levels of IL-10. Additionally, we analysed the expression of cytokines that have been associated with regulation of inflammation in the lung.…”

Section: Resultscontrasting

confidence: 52%

“…We have previously shown that a subpopulation of CD4+ CD25+ FoxP3+ T-lymphocytes have regulatory functions and depend on CCR9 expression to control pathogen-induced inflammation in the gut [ 17 ]. Therefore, the aim of this work was to analyse the role of CCR9 in regulating cell recruitment and modulating the inflammatory process during airway sensitization.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

CCR9 Is a Key Regulator of Early Phases of Allergic Airway Inflammation

López-Pacheco

Soldevila

Pont

et al. 2016

Mediators of Inflammation

Self Cite

View full text Add to dashboard Cite

Airway inflammation is the most common hallmark of allergic asthma. Chemokine receptors involved in leukocyte recruitment are closely related to the pathology in asthma. CCR9 has been described as a homeostatic and inflammatory chemokine receptor, but its role and that of its ligand CCL25 during lung inflammation remain unknown. To investigate the role of CCR9 as a modulator of airway inflammation, we established an OVA-induced allergic inflammation model in CCR9-deficient mice. Here, we report the expression of CCR9 and CCL25 as early as 6 hours post-OVA challenge in eosinophils and T-lymphocytes. Moreover, in challenged CCR9-deficient mice, cell recruitment was impaired at peribronchial and perivenular levels. OVA-administration in CCR9-deficient mice leads to a less inflammatory cell recruitment, which modifies the expression of IL-10, CCL11, and CCL25 at 24 hours after OVA challenge. In contrast, the secretion of IL-4 and IL-5 was not affected in CCR9-deficient mice compared to WT mice. These results demonstrate for the first time that CCR9 and CCL25 expressions are induced in the early stages of airway inflammation and they have an important role modulating eosinophils and lymphocytes recruitment at the first stages of inflammatory process, suggesting that they might be a potential target to regulate inflammation in asthma.

show abstract

Section: Resultscontrasting

confidence: 52%

Section: Introductionmentioning

confidence: 99%

CCR9 Is a Key Regulator of Early Phases of Allergic Airway Inflammation

López-Pacheco

Soldevila

Pont

et al. 2016

Mediators of Inflammation

Self Cite

View full text Add to dashboard Cite

show abstract

“…Following treatment of onchocerciasis patients with ivermectin, Eotaxin-2/CCL24 and MCP-4/CCL13 enhanced suggesting that these chemokines facilitated clearance of O. volvulus microfilariae by monocytes and eosinophil granulocytes [47]. Interestingly, protozoan Entamoeba- specific antigens depressed both Eotaxin-2/CCL24 and MCP-4/CCL13 in adults and the elderly, but not in children and neonates; such depressed responsiveness might support control E. histolytica infection, as elevated levels of Eotaxins were observed in mice with persistent E. histolytica infection [48]. The chemokine MCP-4/CCL13 attracts granulocytes, monocytes, and T cells, and it has been proposed as a biomarker in asthma [49] being up-regulated during both Th1- and Th2-type hyper-responses [10].…”

Section: Discussionmentioning

confidence: 99%

Cytokine and chemokine responses to helminth and protozoan parasites and to fungus and mite allergens in neonates, children, adults, and the elderly

et al. 2013

View full text Add to dashboard Cite

BackgroundIn rural sub-Saharan Africa, endemic populations are often infected concurrently with several intestinal and intravascular helminth and protozoan parasites. A specific, balanced and, to an extent, protective immunity will develop over time in response to repeated parasite encounters, with immune responses initially being poorly adapted and non-protective. The cellular production of pro-inflammatory and regulatory cytokines and chemokines in response to helminth, protozoan antigens and ubiquitous allergens were studied in neonates, children, adults and the elderly.ResultsIn children schistosomiasis prevailed (33%) while hookworm and Entamoeba histolytica/E. dispar was found in up to half of adults and the elderly. Mansonella perstans filariasis was only present in adults (24%) and the elderly (25%). Two or more parasite infections were diagnosed in 41% of children, while such polyparasitism was present in 34% and 38% of adults and the elderly. Cytokine and chemokine production was distinctively inducible by parasite antigens; pro-inflammatory Th2-type cytokine IL-19 was activated by Entamoeba and Ascaris antigens, being low in neonates and children while IL-19 production enhanced “stepwise” in adults and elderly. In contrast, highest production of MIP-1delta/CCL15 was present in neonates and children and inducible by Entamoeba-specific antigens only. Adults and the elderly had enhanced regulatory IL-27 cytokine responses, with Th2-type chemokines (MCP-4/CCL13, Eotaxin-2/CCL24) and cytokines (IL-33) being notably inducible by helminth- and Entamoeba-specific antigens and fungus-derived allergens. The lower cellular responsiveness in neonates and children highlighted the development of a parasite-specific cellular response profile in response to repeated episodes of exposure and re-infection.ConclusionsFollowing repeated exposure to parasites, and as a consequence of host inability to prevent or eliminate intestinal helminth or protozoa infections, a repertoire of immune responses will evolve with lessened pro-inflammatory and pronounced regulatory cytokines and chemokines; this is required for partial parasite control as well as for preventing inadequate and excessive host tissue and organ damage.

show abstract

“…On the one hand, a proinflammatory response that involves cell-mediated immunity and gamma interferon (IFN-␥) has been shown to be protective against E. histolytica (58-61). On the other hand, it is postulated that too robust an immune response augments disease by exacerbation of tissue damage, allowing further invasion of E. histolytica into the colonic epithelium (58,61). For example, increased levels of tumor necrosis factor alpha (TNF-␣), a proinflammatory cytokine, are associated with symptomatic and recurrent E. histolytica infections (62).…”

Section: Discussionmentioning

confidence: 99%

Effect of the Leptin Receptor Q223R Polymorphism on the Host Transcriptome following Infection with Entamoeba histolytica

et al. 2013

View full text Add to dashboard Cite

dResistance to amebiasis is associated with a polymorphism in the leptin receptor. Previous studies demonstrated that humans with the ancestral Q223 leptin receptor allele were nearly four times less likely to be infected with Entamoeba histolytica than those carrying the mutant R223 allele. We hypothesized that the Q223 allele protected against E. histolytica via STAT3-mediated transcription of genes required for mucosal immunity. To test this, mice containing the humanized LEPR Q or R allele at codon 223 were intracecally infected with E. histolytica. Susceptibility to amebiasis was assessed, and cecal tissues were analyzed for changes in gene expression. By 72 h postchallenge, all Q223 mice had cleared E. histolytica, whereas 39% of 223R mice were infected. Thirty-seven genes were differentially expressed in response to infection at 72 h, including proinflammatory genes (CXCL2, S100A8/9, PLA2G7, ITBG2, and MMP9) and functions pertaining to the movement and activity of immune cells. A comparison at 12 h postchallenge of infected Q223 versus R223 mice identified a subset of differentially expressed genes, many of which were closely linked to leptin signaling. Further analyses indicated that the Q223 gene expression pattern was consistent with a suppressed apoptotic response to infection, while 223R showed increased cellular proliferation and recruitment. These studies are the first to illuminate the downstream effects of leptin receptor polymorphisms on intestinal infection by E. histolytica. As such, they are important for the insight that they provide into this previously uncharacterized mechanism of mucosal immunity.T he association of leptin signaling with infectious diseases has long been suspected; however, only recently was the significant association between leptin and human disease described (1-4). It was determined that a common genetic mutation of the leptin receptor (LEPR), Q223R, was associated with an approximately 4-fold increase in likelihood of infection with Entamoeba histolytica in a Bangladeshi cohort of children (4). The murine model of amebiasis recapitulated the human findings, demonstrating that 223R (homozygous for arginine) mice were significantly more susceptible to infection with E. histolytica than Q223 (homozygous for glutamine) mice. In addition, both ob/ob (leptin Ϫ/Ϫ ) and db/db (LEPR Ϫ/Ϫ ) mice had increased rates of E. histolytica infection and worse tissue destruction and mortality. Finally, the use of tissue-specific LEPR knockouts demonstrated that the site of action for LEPR was located within the intestinal epithelial cell (IEC) population (5).LEPR belongs to the gp130 family of cytokine receptors. Upon leptin binding to the homodimeric LEPR, Janus kinase 2 (JAK2) is activated, leading to the phosphorylation of tyrosines 985, 1077, and 1138 on LEPR, which in turn are recognized by Src homology 2 domain-containing tyrosine phosphatase (SHP2) and suppressor of cytokine signaling 3 (SOCS3), STAT5a/b, and STAT3 (respectively) (6)(7)(8). Murine studies demonstrated that signal...

show abstract

CCR9+ T cells contribute to the resolution of the inflammatory response in a mouse model of intestinal amoebiasis

Cited by 12 publications

References 64 publications

CCR9 Is a Key Regulator of Early Phases of Allergic Airway Inflammation

CCR9 Is a Key Regulator of Early Phases of Allergic Airway Inflammation

Cytokine and chemokine responses to helminth and protozoan parasites and to fungus and mite allergens in neonates, children, adults, and the elderly

Effect of the Leptin Receptor Q223R Polymorphism on the Host Transcriptome following Infection with Entamoeba histolytica

Contact Info

Product

Resources

About