ARTICLES response through the oral delivery of bacterial extracts. This procedure is a common practice in Europe to reduce the clinical symptoms, the incidence, the duration, and the severity of disease in patients suffering from recurrent respiratory infections. 11,12 According to the concept of " common mucosal immune system, " presentation of an antigen at one mucosal site leads to the stimulation of an immune response at a distant mucosal site. Similarly, oral treatment with bacterial extracts modulates both systemic and local immune responses. 13 However, the mechanisms underlying the immunostimulatory effect of these bacterial extracts via the gastrointestinal route remain unclear. Broncho-Vaxom (BV) is an endotoxin-low, lyophilized fractionated alkaline extract of the following eight bacterial strains: Haemophilus influenzae , Diplococcus pneumonia , Klebsiella pneumoniae , Klebsiella ozaenae , Staphylococcus aureus , Streptococcus pyogenes , Streptococcus viridans , and Neisseria catarrhalis. It has been widely used in children and adults suffering from repeated upper respiratory tract infections, 14-16 and it efficiently reduces both the frequency and the duration of the infections. 12 In the present report, we have investigated the effect of oral BV administration in the development of allergic airway inflammation. To this aim, BALB / c mice were treated with BV orally, and subsequently sensitized and challenged with the Leishmania homolog of receptors for activated c kinase (LACK) antigen 17 or with the commonly used OVA antigen. RESULTS Oral administration of BV protects mice from allergic airway inflammation
The intestinal microbiota plays a critical role in the development of the immune system. Recent investigations have highlighted the potential of helminth therapy for treating a range of inflammatory disorders, including celiac disease (CeD); however, the mechanisms by which helminths modulate the immune response of the human host and ameliorate CeD pathology are unknown. In this study, we investigated the potential role of alterations in the human gut microbiota in helminth-mediated suppression of an inflammatory disease. We assessed the qualitative and quantitative changes in the microbiota of human volunteers with CeD prior to and following infection with human hookworms, and following challenge with escalating doses of dietary gluten. Experimental hookworm infection of the trial subjects resulted in maintenance of the composition of the intestinal flora, even after a moderate gluten challenge. Notably, we observed a significant increase in microbial species richness over the course of the trial, which could represent a potential mechanism by which hookworms can regulate gluten-induced inflammation and maintain intestinal immune homeostasis.
In the developed world, declining prevalence of some parasitic infections correlates with increased incidence of allergic and autoimmune disorders. Moreover, experimental human infection with some parasitic worms confers protection against inflammatory diseases in phase 2 clinical trials. Parasitic worms manipulate the immune system by secreting immunoregulatory molecules that offer promise as a novel therapeutic modality for inflammatory diseases. We identify a protein secreted by hookworms, anti-inflammatory protein-2 (AIP-2), that suppressed airway inflammation in a mouse model of asthma, reduced expression of costimulatory markers on human dendritic cells (DCs), and suppressed proliferation ex vivo of T cells from human subjects with house dust mite allergy. In mice, AIP-2 was primarily captured by mesenteric CD103 DCs and suppression of airway inflammation was dependent on both DCs and Foxp3 regulatory T cells (T) that originated in the mesenteric lymph nodes (MLNs) and accumulated in distant mucosal sites. Transplantation of MLNs from AIP-2-treated mice into naïve hosts revealed a lymphoid tissue conditioning that promoted T induction and long-term maintenance. Our findings indicate that recombinant AIP-2 could serve as a novel curative therapeutic for allergic asthma and potentially other inflammatory diseases.
BackgroundResident memory T cells have emerged as key players in the immune response generated against a number of pathogens. Their ability to take residence in non-lymphoid peripheral tissues allows for the rapid deployment of secondary effector responses at the site of pathogen entry. This ability to provide enhanced regional immunity has gathered much attention, with the generation of resident memory T cells being the goal of many novel vaccines.ObjectivesThis review aimed to systematically analyze published literature investigating the role of resident memory T cells in human infectious diseases. Known effector responses mounted by these cells are summarized and key strategies that are potentially influential in the rational design of resident memory T cell inducing vaccines have also been highlighted.MethodsA Boolean search was applied to Medline, SCOPUS, and Web of Science. Studies that investigated the effector response generated by resident memory T cells and/or evaluated strategies for inducing these cells were included irrespective of published date. Studies must have utilized an established technique for identifying resident memory T cells such as T cell phenotyping.ResultsWhile over 600 publications were revealed by the search, 147 articles were eligible for inclusion. The reference lists of included articles were also screened for other eligible publications. This resulted in the inclusion of publications that studied resident memory T cells in the context of over 25 human pathogens. The vast majority of studies were conducted in mouse models and demonstrated that resident memory T cells mount protective immune responses.ConclusionAlthough the role resident memory T cells play in providing immunity varies depending on the pathogen and anatomical location they resided in, the evidence overall suggests that these cells are vital for the timely and optimal protection against a number of infectious diseases. The induction of resident memory T cells should be further investigated and seriously considered when designing new vaccines.
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