Human IL-4 macrophages promote epithelial wound recovery and suppress colitis, supporting their use as a cell therapy for IBD.

Abstract Background Studies on the inhibition of inflammation by infection with helminth parasites have, until recently, overlooked a key determinant health: gut microbiota. Infection helminths evokes changes in composition their host’s microbiota: one outcome which is an altered metabolome (e.g., levels short-chain fatty acids (SCFAs)) lumen. The functional implications helminth-evoked enteric microbiome (composition and metabolites) are poorly understood explored respect to controlling...

Chronic inflammation of the intestinal mucosa is characteristic inflammatory bowel diseases such as ulcerative colitis and Crohn’s disease. Helminth parasites have developed immunomodulatory strategies that may impact outcome several diseases. Therefore, we investigated whether Taenia crassiceps infection able to decrease effects dextran sulfate sodium- (DSS-) induced in BALB/c C57BL/6 mice. Preinfection significantly reduced manifestations DSS-induced colitis, weight loss shortened colon...

Inflammation is currently considered a hallmark of cancer and plays decisive role in different stages tumorigenesis, including initiation, promotion, progression, metastasis resistance to antitumor therapies. Colorectal disease widely associated with local chronic inflammation. Additionally, extrinsic factors such as infection may beneficially or detrimentally alter progression. Several reports have noted the ability various parasitic infections modulate development, favoring tumor...

Colorectal cancer (CRC) is one of the most widespread and deadly types neoplasia around world, where inflammatory microenvironment has critical importance in process tumor growth, metastasis, drug resistance. Despite its limited effectiveness, 5-fluorouracil (5-FU) main utilized for CRC treatment. The combination 5-FU with other agents modestly increases effectiveness patients. Here, we evaluated anti-inflammatory Trimethylglycine Signal transducer activator transcription (STAT6) inhibitor...

Colitis-associated colorectal cancer (CAC) is one of the most common cancers and closely related to chronic or deregulated inflammation.Helminthic infections can modulate inflammatory responses in some diseases, but their immunomodulatory role during development remains completely unknown.We have analyzed Taenia crassiceps-induced anti-inflammatory response determining outcome CAC.We show that extraintestinal T. crassiceps infection CAC mice inhibited colonic tumor formation prevented goblet...

Signal transducer and activator of transcription 1 (STAT1) is part the Janus kinase (JAK/STAT) signaling pathway that controls critical events in intestinal immune function related to innate adaptive immunity. Recent studies have implicated STAT1 tumor–stroma interactions, its expression activity are perturbed during colon cancer. However, role initiation inflammation-associated cancer not clearly understood. To determine colitis-associated colorectal (CAC), we analyzed tumor development...

Abstract Intestinal cell death is a defining feature of Crohn’s disease (CD), major form inflammatory bowel disease. The focus on this aspect enteric inflammation has mainly been epithelial cells, while other types such as stromal and myeloid cells have received less attention. Hypothesising that decreased macrophage viability in an oxidative environment could be contributing factor to the pathophysiology CD, we found monocyte-derived macrophages from individuals with active CD (but not...

Signal transducer and activator of transcription 1 (STAT1) acts as a tumor suppressor molecule in colitis-associated colorectal cancer (CAC), particularly during the very early stages, modulating immune responses controlling mechanisms such apoptosis cell proliferation. Previously, using an experimental model CAC, we reported increased intestinal proliferation faster development, which were consistent with more signs disease damage, reduced survival STAT1-/- mice, compared WT counterparts....

Helminth parasites modulate immune responses in their host to prevent elimination and establish chronic infections. Our previous studies indicate that Taenia crassiceps-excreted/secreted antigens (TcES) downregulate inflammatory rodent models of autoimmune diseases, by promoting the generation alternatively activated-like macrophages (M2) vivo. However, molecular mechanisms triggered TcES macrophage polarization response remain unclear. Here, we found that, while reduced production cytokines...

The murine interleukin-4 treated macrophage (MIL4) exerts anti-inflammatory and pro-healing effects has been shown to reduce the severity of chemical-induced colitis. Positing M(IL4) transfer as an therapy, possibility side-effects must be considered. Consequently, bone marrow-derived M(IL4)s were administered via intraperitoneal injection mice concomitant with Citrobacter rodentium infection (infections colitis), azoxymethane/dextran sodium sulphate (AOM/DSS) treatment [a model colorectal...

Recognizing that enteric tuft cells can signal the presence of nematode parasites, we investigated whether are required for expulsion cestode, Hymenolepis diminuta , from non-permissive mouse host, and in concomitant anti-helminthic responses. BALB/c C57BL/6 mice infected with H . expelled worms by 11 days post-infection (dpi) displayed DCLK1 + (doublecortin-like kinase 1) cell hyperplasia small intestine (not colon) at dpi. This was dependent on IL-4R α signalling adaptive immunity, but not...

<title>Abstract</title> Intestinal cell death is a defining feature of Crohn’s disease (CD), major form inflammatory bowel disease. The focus on this aspect enteric inflammation has mainly been epithelial cells, while other types such as stromal and myeloid cells have received less attention. Hypothesising that decreased macrophage viability in an oxidative environment could be contributing factor to the pathophysiology CD, we found monocyte-derived macrophages from individuals with active...

Interleukin-4 activated human macrophages (M(IL4) promote epithelial wound healing and exert an anti-colitic effect in a murine model. Blood monocyte-derived M(IL4)s from healthy donors individuals with Crohn's disease had increased mRNA expression of the calcitonin gene-related peptide (CGRP) receptor chain, RAMP1, raising issue neural modulation reparative function. Thus, (MIL4)s were treated CGRP cells phagocytotic, repair functions assessed. Initial studies confirmed up-regulation...

Abstract A role for chronic inflammation in tumor development has been well established and supported both, animal epidemiological studies. classic association between cancer is colitis-associated colorectal (CAC). Helminth infections helminth-derived molecules have recognized as inducers of immunoregulation. Taenia crassiceps modulates inflammatory diseases such type 1 diabetes, colitis, autoimmune encephalomyelitis. Here we analyzed the pathophysiologic implication T. excreted/secreted...

Abstract Whereas a causal association between viral and bacterial infections with tumor development has been well established in animal epidemiological studies, the impact of parasitic cancer is almost unknown. Evidences indicate that can be triggered by chronic or deregulated inflammatory processes, such as colitis-associated colorectal (CAC). Using helminth infection model, we have analyzed role helminth-induced anti-inflammatory response determining outcome CAC. Following Taenia...

Abstract Alternatively activated macrophages (aaMφ) are key players in the immunomodulation generated during helminth infections. Recent evidences suggest that derived molecules from helminths can directly induce aaMφ. Taenia crassiceps and its excreted/secreted products (TcES) have been demonstrated modulate inflammatory responses. We special interest determine whether TcES capable of generate On other side, ability microRNAs (miRNAs) to influence cellular functions their development...

Whereas a causal association between viral and bacterial infections with tumor development has been well established in animal epidemiological studies, the impact of parasitic cancer is almost unknown. Evidences indicate that can be triggered by chronic or deregulated inflammatory processes, such as colitis‐associated colorectal (CAC). Using helminth infection model, we have analyzed role helminth‐induced anti‐inflammatory response determining outcome CAC. Following Taenia crassiceps CAC,...

Abstract Toxocariasis is a worldwide zoonotic parasitic disease caused by Toxocara canis. Infection accidental ingestion of embryonated eggs, which hatch and the liberated larvae migrate to different organs. In murine models causes transitory hemorrhagic pulmonary lesions associated with strong TH2 responses heavy parasite burdens. Alternatively activated macrophages (aaM), through STAT6 signaling, are involved in tissue repair, but its role T. canis infection has not been determined yet. On...

Abstract Helminth parasites bias the immune response toward Th2 and/or to a regulatory environment associated with high levels of IL-4, IL-13, IL-5 and IL-10. In addition, helminth infections impair immunity against other unrelated infections. Thus, helminths can modulate in their host, they have multiple ways escape or system. One potential evasion strategies involves modulating early macrophages dendritic cells (DCs). These modulatory activities been exploited interferer development...