Synergistic and antagonistic interaction between different branches of the immune system is related to melanin-based coloration in nestling tawny owls.

When exposed to parasites, hosts often mount energetically expensive immune responses, and this may alter resource allocation between competing life history traits including other components of the immune system. Here, we investigated whether a humoral immune challenge towards a vaccine reduces or enhances the cutaneous immune responses towards an injection of lipopolysaccharid (LPS, innate immunity) and phytohaemagglutinin (PHA, T-cell immunity) in nestling tawny owls in interaction with the degree of plumage melanin-based coloration. The humoral immune challenge enhanced the response to LPS similarly in differently coloured nestlings. In contrast, the same humoral immune challenge enhanced immune response to PHA in dark reddish melanic nestlings while reducing it in pale reddish melanic nestlings. Our results highlight that both antagonistic and synergistic interactions can take place among branches of immune system, and that the sign and magnitude of these interactions can vary with immune responses involved and the degree of melanin-based coloration.

The effects of cocoa on the immune system

Cocoa is a food relatively rich in polyphenols, which makes it a potent antioxidant. Due to its activity as an antioxidant, as well as through other mechanisms, cocoa consumption has been reported to be beneficial for cardiovascular health, brain functions, and cancer prevention. Furthermore, cocoa influences the immune system, in particular the inflammatory innate response and the systemic and intestinal adaptive immune response. Preclinical studies have demonstrated that a cocoa-enriched diet modifies T-cell functions that conduce to a modulation of the synthesis of systemic and gut antibodies. In this regard, it seems that a cocoa diet in rats produces changes in the lymphocyte composition of secondary lymphoid tissues and the cytokines secreted by T cells. These results suggest that it is possible that cocoa could inhibit the function of Th2 cells, and in line with this, the preventive effect of cocoa on IgE synthesis in a rat allergy model has been reported, which opens up new perspectives when considering the beneficial effects of cocoa compounds. On the other hand, cocoa intake modifies the functionality of gut-associated lymphoid tissue by means of modulating IgA secretion and intestinal microbiota. The mechanisms involved in these influences are discussed here. Further research may elucidate the cocoa compounds involved in such an effect and also the possible medical approaches to these repercussions

Propolis and the immune system: a review

Propolis has been used empirically for centuries and it was always mentioned as an immunomodulatory agent. In recent years, in vitro and in vivo assays provided new information concerning its mechanisms of action, thus a review dealing with propolis and the immune system became imperative. This review compiles data from our laboratory as well as from other researchers, focusing on its chemical composition and botanical sources, the seasonal effect on its composition and biological properties, its immunomodulatory and antitumor properties, considering its effects on antibody production and on different cells of the immune system, involving the innate and adaptive immune response. In vitro and in vivo assays demonstrated the modulatory action of propolis on murine peritoneal macrophages, increasing their microbicidal activity. Its stimulant action on the lytic activity of natural killer cells against tumor cells, and on antibody production was demonstrated. Propolis inhibitory effects on lymphoproliferation may be associated to its anti-inflammatory property. In immunological assays, the best results were observed when propolis was administered over a short-term to animals. Propolis antitumor property and its anticarcinogenic and antimutagenic potential are discussed. Since humans have used propolis for different purposes and propolis-containing products have been marketed, the knowledge of its properties with scientific basis is not only of academic interest but also of those who use propolis as well. This review opens a new perspective on the investigation of propolis biological properties, mainly with respect to the immune system. (c) 2007 Elsevier B.V.. All rights reserved.

Role of TLR-2 and fungal surface antigens on innate immune response against Sporothrix schenckii

Sporotrichosis is an infection caused by the dimorphic fungus Sporothrix schenckii. Toll-like receptors (TLRs) play an important role in immunity, since they bind to pathogen surface antigens and initiate the immune response. However, little is known about the role of TLR-2 and fungal surface antigens in the recognition of S. schenckii and in the subsequent immune response. This study aimed to evaluate the involvement of TLR-2 and fungal surface soluble (SolAg) and lipidic (LipAg) antigens in phagocytosis of S. schenckii and production of immune mediators by macrophages obtained from WT and TLR-2 -/- animals. The results showed that TLR-2-/- animals had had statistical lower percentage of macrophages with internalized yeasts compared to WT. SolAg and LipAg impaired phagocytosis and immunological mediator production for both WT and TLR-2-/-. The absence of TLR-2 led to lower production of the cytokines TNF, IL-1β, IL-12 and IL-10 compared to WT animals. These results suggest a new insight in relation to how the immune system, through TLR-2, recognizes and induces the production of mediators in response to the fungus S. schenckii. Copyright © Informa Healthcare USA, Inc.

The immune system is limited by oxidative stress: dietary selenium promotes optimal antioxidative status and greatest immune defense in pacu Piaractus mesopotamicus

Reactive oxygen species (ROS) are reactive molecules containing oxygen, that form as byproducts of aerobic metabolism, including immune system processes. Too much ROS may cause oxidative stress. In this study, we examined whether it can also limit the production of immune system compounds. To assess the relationship between antioxidant status and immunity we evaluated the effect of dietary supplementation with organic selenium, given at various levels for 10 days, on the antioxidant and immune system of the pacu fish (Piaractus mesopotamicus). Fish fed a diet containing 0.6 mg Se-yeast kg(-1) showed significant improvement in antioxidant status, as well as in hematological and immunological profiles. Specifically, they had the highest counts for catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), red blood cells, and thrombocytes; the highest leukocyte count (particularly for monocytes); and the highest serum lysozyme activity. There was also a positive correlation between GPx and lysozyme in this group of fish. These findings indicate that short-term supplementation with 0.6 mg Se-yeast kg(-1) reestablished the antioxidative status, allowing the production of innate components which can boost immunity without the risk of oxidative stress. This study shows a relationship between oxidative stress and immunity, and, from a practical perspective, shows that improving immunity and health in pacu through the administration of selenium could improve their growth performance.

The neonatal immune system: immunomodulation of infections in early life

The innate and adaptive immune responses in neonates are usually functionally impaired when compared with their adult counterparts. The qualitative and quantitative differences in the neonatal immune response put them at risk for the development of bacterial and viral infections, resulting in increased mortality. Newborns often exhibit decreased production of Th1-polarizing cytokines and are biased toward Th2-type responses. Studies aimed at understanding the plasticity of the immune response in the neonatal and early infant periods or that seek to improve neonatal innate immune function with adjuvants or special formulations are crucial for preventing the infectious disease burden in this susceptible group. Considerable studies focused on identifying potential immunomodulatory therapies have been performed in murine models. This article highlights the strategies used in the emerging field of immunomodulation in bacterial and viral pathogens, focusing on preclinical studies carried out in animal models with particular emphasis on neonatal-specific immune deficits.

[How the bovine viral diarrhea virus outwits the immune system]

The interaction of bovine viral diarrhea virus (BVD virus) with its host has several unique features, most notably the capacity to infect its host either transiently or persistently. The transient infection stimulates an antiviral immune reaction similar to that seen in other transient viral infections. In contrast, being associated with immunotolerance specific for the infecting BVD viral strain, the persistent infection differs fundamentally from other persistent infections like those caused by lentiviruses. Whereas the latter are characterized by complex viral evasion of the host's adaptive immune response by mechanisms such as antigenic drift and interference with presentation of T cell epitopes, BVD virus avoids the immune response altogether by inducing both humoral and cellular immune tolerance. This is made possible by invasion of the fetus at an early stage of development. In addition to adaptive immunity, BVD virus also manipulates key elements of the host's innate immune response. The non-cytopathic biotype of BVD virus, which is capable of persistently infecting its host, fails to induce type I interferon. In addition, persistently infected cells are resistant to the induction of apoptosis by double-stranded RNA and do not produce interferon when treated with this pathogen-associated molecular pattern (PAMP) that signals viral infection. Moreover, when treated with interferon, cells persistently infected with non-cytopathic BVD virus do not clear the virus. Surprisingly, however, despite this lack of effect on persistent infection, interferon readily induces an antiviral state in these cells, as shown by the protection against infection by unrelated viruses. Overall, BVD virus manipulates the host's interferon defense in a manner that optimises its chances of maintaining the persistent infection as well as decreasing the risks that heterologous viral infections may carry for the host. Thus, since not all potential host cells are infected in animals persistently infected with BVD virus, heterologous viruses replicating in cells uninfected with BVD virus will still trigger production of interferon. Interferon produced by such cells will curtail the replication of heterologous viruses only, be that in cells already infected with BVD virus, or in cells in which the heterologous virus may replicate alone. From an evolutionary viewpoint, this strategy clearly enhances the chances of transmission of BVD virus to new hosts, as it attenuates the negative effects that a global immunosuppression would have on the survival of persistently infected animals.

Potent innate immune response to pathogenic leptospira in human whole blood.

BACKGROUND Leptospirosis is caused by pathogenic spirochetes of the genus Leptospira. The bacteria enter the human body via abraded skin or mucous membranes and may disseminate throughout. In general the clinical picture is mild but some patients develop rapidly progressive, severe disease with a high case fatality rate. Not much is known about the innate immune response to leptospires during haematogenous dissemination. Previous work showed that a human THP-1 cell line recognized heat-killed leptospires and leptospiral LPS through TLR2 instead of TLR4. The LPS of virulent leptospires displayed a lower potency to trigger TNF production by THP-1 cells compared to LPS of non-virulent leptospires. METHODOLOGY/PRINCIPAL FINDINGS We investigated the host response and killing of virulent and non-virulent Leptospira of different serovars by human THP-1 cells, human PBMC's and human whole blood. Virulence of each leptospiral strain was tested in a well accepted standard guinea pig model. Virulent leptospires displayed complement resistance in human serum and whole blood while in-vitro attenuated non-virulent leptospires were rapidly killed in a complement dependent manner. In vitro stimulation of THP-1 and PBMC's with heat-killed and living leptospires showed differential serovar and cell type dependence of cytokine induction. However, at low, physiological, leptospiral dose, living virulent complement resistant strains were consistently more potent in whole blood stimulations than the corresponding non-virulent complement sensitive strains. At higher dose living virulent and non-virulent leptospires were equipotent in whole blood. Inhibition of different TLRs indicated that both TLR2 and TLR4 as well as TLR5 play a role in the whole blood cytokine response to living leptospires. CONCLUSIONS/SIGNIFICANCE Thus, in a minimally altered system as human whole blood, highly virulent Leptospira are potent inducers of the cytokine response.

Multiple roles of complement MASP-1 at the interface of innate immune response and coagulation

MASP-1 is a versatile serine protease that cleaves a number of substrates in human blood. In recent years it became evident that besides playing a crucial role in complement activation MASP-1 also triggers other cascade systems and even cells to mount a more powerful innate immune response. In this review we summarize the latest discoveries about the diverse functions of this multi-faceted protease. Recent studies revealed that among MBL-associated serine proteases, MASP-1 is the one responsible for triggering the lectin pathway via its ability to rapidly autoactivate then cleave MASP-2, and possibly MASP-3. The crystal structure of MASP-1 explains its more relaxed substrate specificity compared to the related complement enzymes. Due to the relaxed specificity, MASP-1 interacts with the coagulation cascade and the kinin generating system, and it can also activate endothelial cells eliciting pro-inflammatory signaling.

B cells as a critical node in the microbiota-host immune system network.

Mutualism with our intestinal microbiota is a prerequisite for healthy existence. This requires physical separation of the majority of the microbiota from the host (by secreted antimicrobials, mucus, and the intestinal epithelium) and active immune control of the low numbers of microbes that overcome these physical and chemical barriers, even in healthy individuals. In this review, we address how B-cell responses to members of the intestinal microbiota form a robust network with mucus, epithelial integrity, follicular helper T cells, innate immunity, and gut-associated lymphoid tissues to maintain host-microbiota mutualism.

Comparison of innate immune responses towards rhinovirus infection of primary nasal and bronchial epithelial cells.

BACKGROUND AND OBJECTIVE Rhinoviruses (RV) replicate in both upper and lower airway epithelial cells. We evaluated the possibility of using nasal epithelial cells (NEC) as surrogate of bronchial epithelial cells (BEC) for RV pathogenesis cell culture studies. METHODS We used primary paired NEC and BEC cultures established from healthy subjects and compared the replication of RV belonging to the major (RV16) and minor (RV1B) group, and the cellular antiviral and proinflammatory cytokine responses towards these viruses. We related antiviral and pro-inflammatory responses of NEC isolated from CF and COPD patients with those of BEC. RESULTS RV16 replication and major group surface receptor (ICAM-1) expression were higher in healthy NEC compared with BEC (P < 0.05); RV1B replication and minor group surface receptor (LDLR) expression were similar. Healthy NEC and BEC produced similar levels of IFN-β and IFN-λ2/3 upon RV infection or after simulation with poly(IC). IL-8 production was similar between healthy NEC and BEC. IL-6 release at baseline (P < 0.01) and upon infection with RV16 (P < 0.05) and poly(IC) stimulation (P < 0.05) was higher in NEC. RV1B viral load in NEC was related to RV1B viral load in BEC (r = 0.49, P = 0.01). There was a good correlation of IFN levels between NEC and BEC (r = 0.66, P = 0.0004 after RV1B infection). IL-8 production in NEC was related to IL-8 production in BEC (r = 0.48, P = 0.02 after RV1B infection). CONCLUSION NEC are a suitable alternative cellular system to BEC to study the pathophysiology of RV infections and particularly to investigate IFN responses induced by RV infection.

A bacterial cysteine protease effector protein interferes with photosynthesis to suppress plant innate immune responses

The bacterial pathogen Pseudomonas syringae pv tomato DC3000 suppresses plant innate immunity with effector proteins injected by a type III secretion system (T3SS). The cysteine protease effector HopN1, which reduces the ability of DC3000 to elicit programmed cell death in non-host tobacco, was found to also suppress the production of defence-associated reactive oxygen species (ROS) and callose when delivered by Pseudomonas fluorescens heterologously expressing a P. syringae T3SS. Purified His 6 -tagged HopN1 was used to identify tomato PsbQ, a member of the oxygen evolving complex of photosystem II (PSII), as an interacting protein. HopN1 localized to chloroplasts and both degraded PsbQ and inhibited PSII activity in chloroplast preparations, whereas a HopN1 D299A non-catalytic mutant lost these abilities. Gene silencing of NtPsbQ in tobacco compromised ROS production and programmed cell death.

SNAREing immunity: the role of SNAREs in the immune system

The trafficking of molecules and membranes within cells is a prerequisite for all aspects of cellular immune functions, including the delivery and recycling of cell-surface proteins, secretion of immune mediators, ingestion of pathogens and activation of lymphocytes. SNARE (soluble-N-ethylmaleimide-sensitive-factor accessory-protein receptor)-family members mediate membrane fusion during all steps of trafficking, and function in almost all aspects of innate and adaptive immune responses. Here, we provide an overview of the roles of SNAREs in immune cells, offering insight into one level at which precision and tight regulation are instilled on immune responses.

Innate immune humoral factors, C1q and factor H, with differential pattern recognition properties, alter macrophage response to carbon nanotubes

Interaction between the complement system and carbon nanotubes (CNTs) can modify their intended biomedical applications. Pristine and derivatised CNTs can activate complement primarily via the classical pathway which enhances uptake of CNTs and suppresses pro-inflammatory response by immune cells. Here, we report that the interaction of C1q, the classical pathway recognition molecule, with CNTs involves charge pattern and classical pathway activation that is partly inhibited by factor H, a complement regulator. C1q and its globular modules, but not factor H, enhanced uptake of CNTs by macrophages and modulated the pro-inflammatory immune response. Thus, soluble complement factors can interact differentially with CNTs and alter the immune response even without complement activation. Coating CNTs with recombinant C1q globular heads offers a novel way of controlling classical pathway activation in nanotherapeutics. Surprisingly, the globular heads also enhance clearance by phagocytes and down-regulate inflammation, suggesting unexpected complexity in receptor interaction. From the Clinical Editor: Carbon nanotubes (CNTs) maybe useful in the clinical setting as targeting drug carriers. However, it is also well known that they can interact and activate the complement system, which may have a negative impact on the applicability of CNTs. In this study, the authors functionalized multi-walled CNT (MWNT), and investigated the interaction with the complement pathway. These studies are important so as to gain further understanding of the underlying mechanism in preparation for future use of CNTs in the clinical setting.