Determination of natural resistance of mice fed dietary lipids to experimental infection induced by Listeria monocytogenes

Current understanding based on the effect of dietary lipid manipulation upon immune system function indicates that fatty acids are involved in the modulation of the immune response through different and complex pathways. Reduction of several immune parameters by fatty acid action may be applied in the treatment of diseases characterised by an overactivation of the immune system. As a consequence, a reduction of host resistance against infectious agents has been reported in animals fed dietary lipids. The present study confirms the action of dietary lipids on the survival of mice infected with the pathogenic bacterium Listeria monocytogenes. A significant increase in peritoneal cells from mice fed a hydrogenated coconut oil diet was found, while a significant reduction of bacterial recovery from spleens of these mice was observed in this group. In addition, both eicosanoid and phospholipase inhibitors did not promote any modification of lymphocyte proliferation from mice fed olive oil or fish oil.     

Modulatory effects of dietary lipids on immune system functions

Dietary lipid manipulation may affect a great number of immune parameters, such as lymphocyte proliferation, cytokine synthesis, natural killer (NK) cell activity, phagocytosis and so on. The immunomodulation induced by dietary fatty acids may be applied in the amelioration of inflammatory disorders, such as autoimmune diseases. However, the mechanisms that participate in these processes are still poorly understood. It is probable that modulation of immune system by fatty acids of the diet may occur by alteration of membrane fluidity, lipid peroxide formation, eicosanoid production or regulation of gene expression. However, recent studies have reported the effects of several free fatty acids on apoptosis induction of in vitro cultures. In fact, a possible explanation of the effects that fatty acids promote on the immune system cells could be associated with an apoptotic process performed in an irreversible way. In vivo studies have demonstrated the ability of fatty acids to alter the survival of animals fed diets containing oils and infected with a pathogenic bacterium. Experimental infection in animals fed dietary lipids produces a modification of resistance to micro-organisms. The present review analyses all of these parameters that dietary fatty acids are capable of altering in order to modify the immune response. Further studies will be needed to establish the mechanisms involved in immune system regulation, reduction of symptoms derived from autoimmune pathologies and so on.     

Immunomodulatory effects of dietary lipids alter host natural resistance of mice to Listeria monocytogenes infection

Over the past two decades, unsaturated fatty acids have received particular attention due to their ability to suppress immune functions. Nevertheless, suppression of immune functions also involves a reduction of host natural resistance to eliminate the infectious agents. We have analyzed the role of dietary lipids on immune functions in cells cultured with Listeria monocytogenes. Bactericidal efficiency of peritoneal cells from mice fed a fish oil diet against this bacterium was reduced and the incubation of peritoneal cells with polyunsaturated fatty acids led to similar results. The levels of superoxide radicals in the presence of L. monocytogenes increased in cells from mice fed olive oil or fish oil diets. Proteasome activity, a mechanism that participates in T cell activation, was inhibited in all of the dietary groups assayed in the presence of L. monocytogenes, but this inhibition was abolished in the presence of both MG132 (a proteasome inhibitor) and L. monocytogenes. Overall, these results underline the potential role of fatty acids in the modulation of many functions of the immune system.     

Lack of Apoptosis in <Emphasis Type="Italic">Listeria monocytogenes</Emphasis>-Infected Thymocytes from Mice Fed with Dietary Lipids

The potential action of certain fatty acids has been studied since the early 1970s. Numerous effects on immune system functions have been related to dietary lipid administration; therefore, several of them have been applied in the treatment of inflammatory disorders. Nevertheless, n-3 polyunsaturated fatty acids may affect host resistance to infectious diseases. In addition, several studies have demonstrated that certain fatty acids are involved in apoptosis induction. Here, we have examined the action of different dietary lipids on the promotion of apoptosis in thymocytes from mice fed with dietary lipids and infected with Listeria monocytogenes. Thus, L. monocytogenes promoted an important cytotoxic effect in all of the groups, but it did not increase the percentage of DNA fragmentation. Similarly, an important increase of caspase-3 activity was demonstrated in OO and FO groups, but infection with L. monocytogenes exerted an inhibitory effect. Finally, L. monocytogenes did not modify proteasome activity among groups fed with dietary lipids. On the basis of this preliminary study, we can state that the infection of thymocytes from mice fed with dietary lipids does not promote a synergistic effect in the induction of apoptosis. Hence, these results may partially serve to elucidate the immune mechanisms involved in cells from mice fed with dietary lipids in an infectious process.     

Changes in the immune functions and susceptibility to Listeria monocytogenes infection in mice fed dietary lipids

The direct examination of the effects that fish oil diets (composed of long-chain n-3 polyunsaturated fatty acids) exert on immune system function indicates a reduction of host natural resistance to infectious diseases mainly because of a suppression of immune function generated by the fatty acids contained in this diet. Here, we evaluated the concentration of IL-12, IL-4, prostaglandin E2 and leukotriene B4 in the serum from BALB/c mice receiving four different diets. Each group was fed a diet that differed only in the source of fat: a low-fat diet (2.5% by weight), an olive oil diet (20% by weight), a fish oil diet (20% by weight) or a hydrogenated coconut oil diet (20% by weight). Mice were fed for 4 weeks and then infected with the intracellular pathogen Listeria monocytogenes. An initial reduction in the Th1-type response as a result of a decrease in IL-12p70 secretion, an inefficient action of IL-4 (Th2-type response) and no modification of pro-inflammatory lipid-mediator production could be, at least in part, the key events responsible for the inadequate elimination of L. monocytogenes from the spleens of mice fed a fish oil diet. Furthermore, our results suggest that the type of dietary lipids may affect the circulating concentration of IL-12p70 and IL-4, leading to a modulation in the protective cellular immune response to L. monocytogenes infection.     

Molecular determinants and regulation of Leishmania virulence

A Leishmania model to explain microbial virulence in chronic infectious diseases is proposed. All these diseases progress from infection to symptomatic phase to host death or recovery. The outcome of each phase is depicted to result from the interactions of a distinct group of parasite molecules with a specific host immune compartment. The first group consists of invasive/evasive determinants, which are largely parasite cell surface and secreted molecules. Their activities help parasites establish infection by overcoming host immunologic and non-immunologic barriers. These determinants do not cause disease per se, but are indispensable for infection necessary for the development of a disease-state. The second group of parasite molecules consists of "pathoantigenic" determinants – unique parasite epitopes present often within otherwise highly conserved cytoplasmic molecules. Immune response against these determinants is thought to result in immunopathology manifested as clinical signs or symptoms, namely the virulent phenotype. The third group of parasite molecules is hypothetically perceived as vaccine determinants. Their interactions with the host immune system lead to the elimination or reduction of parasites to effect a clinical cure. Differential expression of these determinants alone by parasites may alter their interactions with the hosts. Virulent phenotype is consequently presented as a spectrum of manifestations from asymptomatic infection to fatality. A secondary level of regulation lies in host genetic and environmental factors. The model suggests that different parasite determinants may be targeted by different strategies to achieve more effective control of leishmaniasis and other similar diseases.     

Circadian orchestration of host and gut microbiota in infection

Circadian rhythms are present in almost every organism and regulate multiple aspects of biological and physiological processes (e.g. metabolism, immune responses, and microbial exposure). There exists a bidirectional circadian interaction between the host and its gut microbiota, and potential circadian orchestration of both host and gut microbiota in response to invading pathogens. In this review, we summarize what is known about these intestinal microbial oscillations and the relationships between host circadian clocks and various infectious agents (bacteria, fungi, parasites, and viruses), and discuss how host circadian clocks prime the immune system to fight pathogen infections as well as the direct effects of circadian clocks on viral activity (e.g. SARS-CoV-2 entry and replication). Finally, we consider strategies employed to realign normal circadian rhythmicity for host health, such as chronotherapy, dietary intervention, good sleep hygiene, and gut microbiota-targeted therapy. We propose that targeting circadian rhythmicity may provide therapeutic opportunities for the treatment of infectious diseases.     

Immune regulation by helminth parasites: cellular and molecular mechanisms

Immunology was founded by studying the body's response to infectious microorganisms, and yet microbial prokaryotes only tell half the story of the immune system. Eukaryotic pathogens--protozoa, helminths, fungi and ectoparasites--have all been powerful selective forces for immune evolution. Often, as with lethal protozoal parasites, the focus has been on acute infections and the inflammatory responses they evoke. Long-lived parasites such as the helminths, however, are more remarkable for their ability to downregulate host immunity, protecting themselves from elimination and minimizing severe pathology in the host.     

The modulation of inflammatory gene expression by lipids: mediation through Toll-like receptors

Toll-like receptors (TLRs) were evolved to detect invading pathogens and to induce innate immune responses in order to mount host defense mechanisms. It becomes apparent that the activation of certain TLRs is also modulated by endogenous molecules including lipid components, fatty acids. Results from epidemiological and animal studies demonstrated that saturated and polyunsaturated dietary fatty acids can differentially modify the risk of development of many chronic diseases. Inflammation is now recognized as an important underlying etiologic condition for the pathogenesis of many chronic diseases. Therefore, if the activation of TLRs and consequent inflammatory and immune responses are differentially modulated by types of lipids in vivo, this would suggest that the risk of the development of chronic inflammatory diseases and the host defense against microbial infection may be modified by the types of dietary fat consumed.     

An Intra-Host Mathematical Model on Interaction Between HIV and Malaria

In this paper a mathematical model is proposed for the interaction of the immune system with HIV viruses and malaria parasites in an individual host. It consists of a system of three coupled ordinary differential equations, which represents the rate of change in the concentration of malaria parasites, HIV viruses and immunity effector within a host, respectively. The theoretical model gives insight into the biological balance between pathogen replication and the immune response to the pathogen: persistence versus elimination of the pathogen, which determines the outcome of infection. Dynamical analysis shows that the outcomes of the interactions between the immune system of the host with either malaria parasites or HIV viruses are dramatic such as malaria infection promoting proliferation of HIV virus, HIV infection increasing the risk from malaria and the immune system of the host failing to keep the diseases under control, etc. The results provide a new perspective for understanding of the complexity mechanisms of the co-infection (or dual infection) with malaria and HIV in a host.     

Do sheep regulate the size of their mallophagan louse populations?

Alternatives to chemicals for controlling parasites are required to minimise problems from resistance, residues in animal products and occupational exposure. Utilisation of host response to parasites through selection of resistant types or vaccination is an appealing option. To date most studies have been with haematophagous or invasive parasites which directly contact elements of the host immune system. Sheep lice (Bovicola ovis) feed superficially on the skin of sheep ingesting lipid, scurf, bacteria and loose stratum corneum squames. Evidence is presented that despite their surface feeding habit Bovicola ovis stimulate an immune response in sheep and that this response may play a part in regulating the size of louse populations.     

The Use of Gas Chromatography to Analyze Compositional Changes of Fatty Acids in Rat Liver Tissue during Pregnancy

Gas chromatography (GC) is a highly sensitive method used to identify and quantify the fatty acid content of lipids from tissues, cells, and plasma/serum, yielding results with high accuracy and high reproducibility. In metabolic and nutrition studies GC allows assessment of changes in fatty acid concentrations following interventions or during changes in physiological state such as pregnancy. Solid phase extraction (SPE) using aminopropyl silica cartridges allows separation of the major lipid classes including triacylglycerols, different phospholipids, and cholesteryl esters (CE). GC combined with SPE was used to analyze the changes in fatty acid composition of the CE fraction in the livers of virgin and pregnant rats that had been fed various high and low fat diets. There are significant diet/pregnancy interaction effects upon the omega-3 and omega-6 fatty acid content of liver CE, indicating that pregnant females have a different response to dietary manipulation than is seen among virgin females.     

The flexibility of Apicomplexa parasites in lipid metabolism

Apicomplexa are obligate intracellular parasites responsible for major human infectious diseases such as toxoplasmosis and malaria, which pose social and economic burdens around the world. To survive and propagate, these parasites need to acquire a significant number of essential biomolecules from their hosts. Among these biomolecules, lipids are a key metabolite required for parasite membrane biogenesis, signaling events, and energy storage. Parasites can either scavenge lipids from their host or synthesize them de novo in a relict plastid, the apicoplast. During their complex life cycle (sexual/asexual/dormant), Apicomplexa infect a large variety of cells and their metabolic flexibility allows them to adapt to different host environments such as low/high fat content or low/high sugar levels. In this review, we discuss the role of lipids in Apicomplexa parasites and summarize recent findings on the metabolic mechanisms in host nutrient adaptation.     

Tumor necrosis factor, interleukin, and interferon induced changes in lipid metabolism as part of host defense.

As the immune response is activated during infection, multiple changes in lipid metabolism, especially increased production of VLDL, occur. Many of the cytokines that mediate the immune response are able to produce such changes in lipid metabolism in vivo. The induction of hypertriglyceridemia or other changes in lipid metabolism during infection do not directly cause the wasting syndrome. It appears that such changes in lipid metabolism may be beneficial to the host, as lipoproteins inactivate a variety of infectious agents. Cytokine-driven hepatic VLDL production during infection most likely represents a part of the acute phase response. The body is thus able to increase serum lipids during infection, or at least maintain triglyceride-rich lipoproteins despite the anorexia of infection. In this manner, the anti-infective, protective effects of lipoproteins are maintained.     

A special issue on ＂Interferons, Cytokines, and Immunity＂

Vertebrates including human employ both innate and adaptive immune responses to defend against pathogen infections and malignancy. Interferons and cytokines play pivotal roles in mediating and coordinating diverse aspects of the host immune response responsible for the clearance of infection and elimination of malignant cells. In addition, abnormal immune and/or inflammatory responses are closely linked to the pathogenesis of various human diseases such as infections, autoimmune diseases and cancer. Thus, a better understanding of these signaling pathways is essential to our efforts in developing more effective regimes to prevent and treat infectious diseases as well as to combat autoimmune diseases and cancer.     

Gut microbes as future therapeutics in treating inflammatory and infectious diseases: Lessons from recent findings

The human gut microbiota has been the interest of extensive research in recent years and our knowledge on using the potential capacity of these microbes are growing rapidly. Microorganisms colonized throughout the gastrointestinal tract of human are coevolved through symbiotic relationship and can influence physiology, metabolism, nutrition and immune functions of an individual. The gut microbes are directly involved in conferring protection against pathogen colonization by inducing direct killing, competing with nutrients and enhancing the response of the gut-associated immune repertoire. Damage in the microbiome (dysbiosis) is linked with several life-threatening outcomes viz. inflammatory bowel disease, cancer, obesity, allergy, and auto-immune disorders. Therefore, the manipulation of human gut microbiota came out as a potential choice for therapeutic intervention of the several human diseases. Herein, we review significant studies emphasizing the influence of the gut microbiota on the regulation of host responses in combating infectious and inflammatory diseases alongside describing the promises of gut microbes as future therapeutics.     

Role of co-stimulation in Leishmaniasis

Leishmania are obligate intracellular parasites that cause a wide spectrum of diseases ranging from cutaneous, mucocutaneous and the visceral kind. Persistence or resolution of leishmaniasis is governed by host immune response. Co-stimulation is an important secondary signal that governs the extent, strength and direction of the immune response that follows. Co-stimulation by CD40, B7 and OX40 family has been shown to influence the outcome following Leishmania infection and manipulation of these pathways has shown promise for use in immune therapy of leishmaniasis. In this review, we discuss the roles of CD40, B7 and OX40 co-stimulatory pathways in regulating immunity to Leishmania and their implications in the treatment of this disease.     

Antigens of trichinella spiralis

Following infection with Trichinella spiralis, the host elicits a strong immune response that causes rapid expulsion of parasites, a reduction in reproductive capacity of the remaining parasites a reduction in the number of larvae recovered from host muscles, and impairment of the mobility of worms in the intestines. The need to identify the antigens that evoke such responses is twofold: (1) to develop immunodiagnostic tools; and (2) to understand the basis of protective immunity. In this review, Yuzo Takahashi describes the antigenic profiles of T. spiralis, emphasizing immunocytochemical findings.     

Setaria digitata secreted filarial lipids modulate IL-12 signaling through JAK-STAT pathway leading to the development of Th1 response

Filariasis is a debilitating parasitic disease in many tropical countries. Despite the highly evolved immune system, the filarial parasites successfully evade host immunity to persist for a sustained period of time. Earlier studies have shown that the filarial parasites achieve this long-term survival through release of immunosuppressive materials in the host. In this study, we show that the secreted filarial lipids (SFL) isolated from Setaria digitata suppress Th1 immune response. While immunization with myelin antigen induces Th1 response in mice, in vitro treatment with SFL resulted in a dose-dependent decrease in myelin antigen-induced proliferation and secretion of IL-12 and IFNgamma. The SFL also inhibited IL-12-induced T cell proliferation and Th1 differentiation in vitro. The inhibition of T cell responses by SFL associates with the blockade of IL-12-induced activation of JAK-STAT signaling pathway in T cells. These findings suggest that the SFL modulates Th1 immune response by blocking IL-12 signaling in T cells and thus play a role in host immune evasion of filarial parasites.     

Innate immunity in aging: impact on macrophage function

Innate and adaptive immune functions decline with age, leading to increased susceptibility to infectious diseases and cancer, and reduced responses to preventive vaccination in the elderly population. Macrophages function as 'pathogen sensors' and play an important role in the initiation of inflammatory responses, elimination of pathogens, manipulation of the adaptive immune response and reparation of damaged tissue. In this paper, we review the literature addressing the impact of aging on the macrophage population.