To examine the function of IL-10 synthesis during early infection with the intracellular protozoan Toxoplasma gondii, IL-10 knockout (KO) mice were inoculated with an avirulent parasite strain (ME-49). In contrast to control littermates that displayed 100% survival, the IL-10-deficient animals succumbed within the first 2 wk of the infection, with no evidence of enhanced parasite proliferation. The mortality in the IL-10 KO mice was associated with enhanced liver pathology characterized by increased cellular infiltration and intense necrosis. Levels of IL-12 and IFN-gamma in sera of infected IL-10-deficient animals were four- to sixfold higher than those in sera from control mice, as were mRNA levels for IFN-gamma, IL-1 beta, TNF-alpha, and IL-12 in lung tissue. Similarly, macrophages from IL-10 KO mice activated in vitro or in vivo with T. gondii produced higher levels of TNF-alpha and IL-12 than macrophages from control animals. Moreover, spleen cells from IL-10 KO mice infected with T. gondii secreted more IFN-gamma than splenocytes from nondeficient animals. In vitro depletion experiments indicated that CD4+ lymphocytes are the major source of the latter cytokine in the spleen cell populations, and in vivo depletion with anti-CD4 Abs protected the IL-10 KO mice from parasite-induced mortality. Together the data suggest that endogenous IL-10 synthesis plays an important role in vivo in down-regulating monokine and IFN-gamma responses to acute intracellular infection, thereby preventing host immunopathology.

In the absence of endogenous IL-10, mice acutely infected with Toxoplasma gondii succumb to a lethal

Short-chain fatty acids (SCFAs) are bacterial fermentation products, which are chemically composed by a carboxylic acid moiety and a small hydrocarbon chain. Among them, acetic, propionic and butyric acids are the most studied, presenting, respectively, two, three and four carbons in their chemical structure. These metabolites are found in high concentrations in the intestinal tract, from where they are uptaken by intestinal epithelial cells (IECs). The SCFAs are partially used as a source of ATP by these cells. In addition, these molecules act as a link between the microbiota and the immune system by modulating different aspects of IECs and leukocytes development, survival and function through activation of G protein coupled receptors (FFAR2, FFAR3, GPR109a and Olfr78) and by modulation of the activity of enzymes and transcription factors including the histone acetyltransferase and deacetylase and the hypoxia-inducible factor. Considering that, it is not a surprise, the fact that these molecules and/or their targets are suggested to have an important role in the maintenance of intestinal homeostasis and that changes in components of this system are associated with pathological conditions including inflammatory bowel disease, obesity and others. The aim of this review is to present a clear and updated description of the effects of the SCFAs derived from bacteria on host immune system, as well as the molecular mechanisms involved on them.

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Regulation of immune cell function by short-chain fatty acids

Advancing our understanding of mechanisms of immune regulation in allergy, asthma, autoimmune diseases, tumor development, organ transplantation, and chronic infections could lead to effective and targeted therapies. Subsets of immune and inflammatory cells interact via ILs and IFNs; reciprocal regulation and counter balance among T(h) and regulatory T cells, as well as subsets of B cells, offer opportunities for immune interventions. Here, we review current knowledge about ILs 1 to 37 and IFN-γ. Our understanding of the effects of ILs has greatly increased since the discoveries of monocyte IL (called IL-1) and lymphocyte IL (called IL-2); more than 40 cytokines are now designated as ILs. Studies of transgenic or knockout mice with altered expression of these cytokines or their receptors and analyses of mutations and polymorphisms in human genes that encode these products have provided important information about IL and IFN functions. We discuss their signaling pathways, cellular sources, targets, roles in immune regulation and cellular networks, roles in allergy and asthma, and roles in defense against infections.

https://www.jacionline.org/article/S0091-6749(10)01949-4/pdf

Interleukins, from 1 to 37, and interferon-γ: receptors, functions, and roles in diseases

Evaluation of the Efficacy of a Probiotic Containing Lactobacillus, Bifidobacterium, Enterococcus, and Pediococcus Strains in Promoting Broiler Performance and Modulating Cecal Microflora Composition and Metabolic Activities

Iconographies supplémentaires de l'article : Interleukins, from 1 to 37, and interferon-γ: Receptors, functions, and roles in diseases

Coccidiosis is recognized as the major parasitic disease of poultry and is caused by the apicomplexan protozoan Eimeria. Coccidiosis seriously impairs the growth and feed utilization of infected animals resulting in loss of productivity. Conventional disease control strategies rely heavily on chemoprophylaxis and, to a certain extent, live vaccines. Combined, these factors inflict tremendous economic losses to the world poultry industry in excess of USD 3 billion annually. Increasing regulations and bans on the use of anticoccidial drugs coupled with the associated costs in developing new drugs and live vaccines increases the need for the development of novel approaches and alternative control strategies for coccidiosis. This paper aims to review the current progress in understanding the host immune response to Eimeria and discuss current and potential strategies being developed for coccidiosis control in poultry.

Poultry coccidiosis: recent advancements in control measures and vaccine development

The domestic chicken is a common model organism for human biological research and of course also forms the basis of a global protein industry. Recent methodological advances have spurred the recognition of microbiomes as complex communities with important influences on the health and disease status of the host. In this minireview, we provide an overview of the current state of knowledge of the chicken gastrointestinal microbiome focusing on spatial and temporal variability, the presence and importance of human pathogens, the influence of the microbiota on the immune system, and the importance of the microbiome for poultry nutrition. Review and meta-analysis of public data showed cecal communities dominated by Firmicutes and Bacteroides at the phylum level, while at finer levels of taxonomic resolution, a phylogenetically diverse assemblage of microorganisms appears to have similar metabolic functions that provide important benefits to the host as inferred from metagenomic data. This observation of functional redundancy may have important implications for management of the microbiome. We foresee advances in strategies to improve gut health in commercial operations through management of the intestinal microbiota as an alternative to in-feed subtherapeutic antibiotics, improvements in pre- and probiotics, improved management of polymicrobial poultry diseases, and better control of human pathogens via colonization reduction or competitive exclusion strategies.

The chicken gastrointestinal microbiome

With the increase in regulations regarding the use of antibiotic growth promoters and the rise in consumer demand for poultry products from ‘Raised Without Antibiotics’ or ‘No Antibiotics Ever’ flocks, the quest for alternative products or approaches has intensified in recent years. A great deal of research has focused on the development of antibiotic alternatives to maintain or improve poultry health and performance. This review describes the potential for the various alternatives available to increase animal productivity and help poultry perform to their genetic potential under existing commercial conditions. The classes of alternatives described include probiotics, prebiotics, synbiotics, organic acids, enzymes, phytogenics, antimicrobial peptides, hyperimmune egg antibodies, bacteriophages, clay, and metals. A brief description of the mechanism of action, efficacy, and advantages and disadvantages of their uses are also presented. Though the beneficial effects of many of the alternatives developed have been well demonstrated, the general consensus is that these products lack consistency and the results vary greatly from farm to farm. Furthermore, their mode of action needs to be better defined. Optimal combinations of various alternatives coupled with good management and husbandry practices will be the key to maximize performance and maintain animal productivity, while we move forward with the ultimate goal of reducing antibiotic use in the animal industry.

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Alternatives to antibiotics for maximizing growth performance and feed efficiency in poultry: a review.

Coccidiosis, an intestinal infection caused by intracellular protozoan parasites belonging to several different species of Eimeria, seriously impairs the growth and feed utilization of livestock and poultry. Host immune responses to coccidial infection are complex. Animals infected with Eimeria spp. produce parasite-specific antibodies in both the circulation and mucosal secretions. However, it appears that antibody-mediated responses play a minor role in protection against coccidiosis. Furthermore, there is increasing evidence that cell-mediated immunity plays a major role in resistance to infection. T lymphocytes appear to respond to coccidial infection through both cytokine production and a direct cytotoxic attack on infected cells. The exact mechanisms by which T cells eliminate the parasites, however, remain unclear. Although limited information is available on the intestinal immune system of chickens, gut lymphoid tissues have evolved specialized features that reflect their role as the first line of defense at mucosal surfaces, including both immunoregulatory cells and effector cells. This review summarizes our current understanding of the avian intestinal immune system and mucosal immune responses to Eimeria spp., providing an overview of the complex cellular and molecular events involved in intestinal immune responses to enteric pathogens.

Avian gut-associated lymphoid tissues and intestinal immune responses to Eimeria parasites.

Intestinal parasitism is a major stress factor leading to malnutrition and lowered performance and production efficiency of livestock and poultry. Coccidiosis is an intestinal infection caused by intracellular protozoan parasites belonging to several different species of Eimeria. Infection with coccidia parasites seriously impairs the growth and feed utilization of chickens and costs the US poultry industry more than $1.5 billion in annual losses. Although acquired immunity to Eimeria develops following natural infection, due to the complex life cycle and intricate host immune response to Eimeria, vaccine development has been difficult and a better understanding of the basic immunobiology of pertinent host-parasite interactions is necessary for developing effective immunological control strategies against coccidiosis. Chickens infected with Eimeria produce parasite specific antibodies in both the circulation and mucosal secretions but humoral immunity plays only a minor role in protection against this disease. Rather, recent evidence implicates cell-mediated immunity as the major factor conferring resistance to coccidiosis. This review will summarize current understanding of the avian intestinal immune system and its response to Eimeria as well as provide a conceptual overview of the complex molecular and cellular events involved in intestinal immunity to coccidiosis. It is anticipated that increased knowledge of the interaction between parasites and host immunity will stimulate the birth of novel immunological and molecular biological concepts in the control of intestinal parasitism.

Hyun S. Lillehoj

Papers

Poultry coccidiosis: recent advancements in control measures and vaccine development

The chicken gastrointestinal microbiome

Alternatives to antibiotics for maximizing growth performance and feed efficiency in poultry: a review.

Avian gut-associated lymphoid tissues and intestinal immune responses to Eimeria parasites.

Intestinal immune responses to coccidiosis