Early immune response following Salmonella enterica subspecies enterica serovar Typhimurium infection in porcine jejunal gut loops

Salmonella enterica subspecies enterica serovar Typhimurium, commonly called S. Typhimurium, can cause intestinal infections in humans and various animal species such as swine. To analyze the host response to Salmonella infection in the pig we used an in vivo gut loop model, which allows the analysis of multiple immune responses within the same animal. Four jejunal gut-loops were each inoculated with 3×108 cfu of S. Typhimurium in 3 one-month-old piglets and mRNA expressions of various cytokines, chemokines, transcription factors, antimicrobial peptides, toll like and chemokine receptors were assessed by quantitative real-time PCR in the Peyer’s patch and the gut wall after 24 h. Several genes such as the newly cloned CCRL1/CCX-CKR were assessed for the first time in the pig at the mRNA level. Pro-inflammatory and T-helper type-1 (Th1) cytokine mRNA were expressed at higher levels in infected compared to non-infected control loops. Similarly, some B cell activation genes, NOD2 and toll like receptor 2 and 4 transcripts were more expressed in both tissues while TLR5 mRNA was down-regulated. Interestingly, CCL25 mRNA expression as well as the mRNA expressions of its receptors CCR9 and CCRL1 were decreased both in the Peyer’s patch and gut wall suggesting a potential Salmonella strategy to reduce lymphocyte homing to the intestine. In conclusion, these results provide insight into the porcine innate mucosal immune response to infection with entero-invasive microorganisms such as S. Typhimurium. In the future, this knowledge should help in the development of improved prophylactic and therapeutic approaches against porcine intestinal S. Typhimurium infections

Vaccine Potentiation by Combination Adjuvants

Adjuvants are crucial components of vaccines. They significantly improve vaccine efficacy by modulating, enhancing, or extending the immune response and at the same time reducing the amount of antigen needed. In contrast to previously licensed adjuvants, current successful adjuvant formulations often consist of several molecules, that when combined, act synergistically by activating a variety of immune mechanisms. These “combination adjuvants” are already registered with several vaccines, both in humans and animals, and novel combination adjuvants are in the pipeline. With improved knowledge of the type of immune responses needed to successfully induce disease protection by vaccination, combination adjuvants are particularly suited to not only enhance, but also direct the immune responses desired to be either Th1-, Th2- or Th17-biased. Indeed, in view of the variety of disease and population targets for vaccine development, a panel of adjuvants will be needed to address different disease targets and populations. Here, we will review well-known and new combination adjuvants already licensed or currently in development—including ISCOMs, liposomes, Adjuvant Systems Montanides, and triple adjuvant combinations—and summarize their performance in preclinical and clinical trials. Several of these combination adjuvants are promising having promoted improved and balanced immune responses

Influence of maternal milk on the instestinal immune response ontogeny of the piglet

Le porcelet a un système immunitaire immature à la naissance, ceci est compensé par la protectionsystémique (colostrum) et humoral (lait) de la mère. Cette immunité passive n’est pas le seul transfertmaternel, la microflore et probablement d’autres substances humorales sont aussi transmis, favorisant ledéveloppement de la réponse immune en Immunoglobuline A (IgA).Lors d’un élevage conventionnel, la réponse IgA se développe autour de 3 semaines. La question est desavoir quelle est l’influence de la durée de lactation sur le développement de l’intestin du jeune porcelet. Pourcela, nous avons définis 3 groupes de porcelets sevrés à 1, 2 et 3 semaines et un groupe contrôle non sevré.Nous avons étudié en cinétique à 7, 14, 21 et 28 jours la concentration en IgA du sang et la microfloreintestinale. De plus, l’analyse du répertoire VDJ (chaîne lourde) des IgA a été réalisée à 28 jours.Les résultats montrent qu’une lactation très réduite (à 1 semaine) provoque, à 21 jours, une déficienceen IgA sériques (spécifiques et totaux) et une diversification de la flore. Il en résulte une plus grande diversitédu répertoire IgA dans le ganglion mésentérique.The neonate piglet has an immature immune system, consequently it receives from its mother asystemic and local mucosal protect via the colostrum and milk respectively. The mother is not contribute onlyby passive immunity but also by transmission of microflora and presumably other humoral substancesfavouring the onset of Immunoglobulin A (IgA) immune response.As IgA response increased in conventional breeding, i.e at 3 weeks of age, we ask the question of theinfluence of suckling onto the IgA development in neonatal gut. For that purpose we defined 3 groups ofpiglets weaned at 1, 2 and 3 weeks and 1 group no weaned. We looked IgA products in blood and intestinalmicroflora at days 7, 14, 21, 28 and the IgA heavy VDJ repertoire development at the same age, day 28.The results show that very short suckling (1 week only) led to lower seric IgA (specific and total)concentration and higher flora diversity, at day 21 and consequently larger IgA diversity in the mesentericlymph node (MLN)

Development of gut immunoglobulin A production in piglet in response to innate and environmental factors

International audienceThe current review focuses on pre- and post-natal development of intestinal immunoglobulin A (IgA) production in pig. IgA production is influenced by intrinsic genetic factors in the foetus as well as extrinsic environmental factors during the post-natal period. At birth, piglets are exposed to new antigens through maternal colostrums/milk as well as exogenous microbiota. This exposure to new antigens is critical for the proper development of the gut mucosal immune system and is characterized mainly by the establishment of IgA response. A second critical period for neonatal intestinal immune system development occurs at weaning time when the gut environment is exposed to new dietary antigens. Neonate needs to establish oral tolerance and in the absence of protective milk need to fight potential new pathogens. To improve knowledge about the immune response in the neonates, it is important to identify intrinsic and extrinsic factors which influence the intestinal immune system development and to elucidate their mechanism of action

Single-Donor and Pooling Strategies for Fecal Microbiota Transfer Product Preparation in Ulcerative Colitis: A Systematic Review and Meta-analysis

International audienceIntroduction: Patients with ulcerative colitis (UC) have a less diverse microbiome than healthy subjects. Multiple studies have evaluated fecal microbiota transfer (FMT) in these patients using different methods of product preparation, doses, and routes of administration. A systematic review and meta-analysis was performed to compare the efficacy of single-donor (SDN) and multidonor (MDN) strategies for product preparation.Methods: Systematic searches were performed in Web of Science, Scopus, PubMed, and Orbit Intelligence for studies comparing FMT products manufactured using SDN or MDN strategies to placebo in patients with UC. Fourteen controlled studies were selected for meta-analysis (10 randomized and 4 nonrandomized). The treatment response was assessed by using fixed- and random-effects models, and the significance of the indirect difference between the interventions was assessed using a network approach.Results: Considering all 14 studies, MDN and SDN were superior to placebo in terms of treatment response (risk ratios [RRs]: 4.41 and 1.57, respectively [P ≤ 0.001 for both]), and MDN was superior to SDN (RR: 2.81, P = 0.005). Meta-analysis of the 10 studies with high quality of evidence showed that MDN was superior to SDN in terms of treatment response (RR: 2.31, P = 0.042). Results were identical for both models.Discussion: There was a significant clinical benefit (remission) for patients with UC who received FMT with products manufactured by MDN strategies. Reduction of donor effect may lead to a gain in microbial diversity that could improve response to treatment. These results may have implications in the treatment approach of other diseases amenable to microbiome manipulation

HIV-1 gp120 envelope glycoprotein determinants for cytokine burst in human monocytes.

The first step of HIV infection involves the interaction of the gp120 envelope glycoprotein to its receptor CD4, mainly expressed on CD4+ T cells. Besides its role on HIV-1 entry, the gp120 has been shown to be involved in the production of IL-1, IL-6, CCL20 and other innate response cytokines by bystander, uninfected CD4+ T cells and monocytes. However, the gp120 determinants involved in these functions are not completely understood. Whether signalling leading to cytokine production is due to CD4 or other receptors is still unclear. Enhanced chemokine receptor binding and subsequent clustering receptors may lead to cytokine production. By using a comprehensive panel of gp120 mutants, here we show that CD4 binding is mandatory for cytokine outburst in monocytes. Our data suggest that targeting monocytes in HIV-infected patients might decrease systemic inflammation and the potential tissue injury associated with the production of inflammatory cytokines. Understanding how gp120 mediates a cytokine burst in monocytes might help develop new approaches to improve the chronic inflammation that persists in these patients despite effective suppression of viremia by antiretroviral therapy