Neutrophils in tuberculosis: friend or foe?

Neutrophils are rapidly recruited to sites of mycobacterial infection, where they phagocytose bacilli. Whether neutrophils can kill mycobacteria in vivo probably depends on the tissue microenvironment, stage of infection, individual host, and infecting organism. The interaction of neutrophils with macrophages, as well as the downstream effects on T cell activity, could result in a range of outcomes from early clearance of infection to dissemination of viable bacteria together with an attenuated acquired immune response. In established disease, neutrophils accumulate in situations of high pathogen load or immunological dysfunction, and are likely to contribute to pathology. These activities may have clinical importance in terms of new treatments, targeted interventions and vaccine strategies.     

The complement system in the peripheral nerve: friend or foe?

The complement (C) system plays a central role in innate immunity and bridges innate and adaptive immune responses. A fine balance of C activation and regulation mediates the elimination of invading pathogens and the protection of the host from excessive C deposition on healthy tissues. If this delicate balance is disrupted, the C system may cause injury and contribute to the pathogenesis of various diseases, including neuropathies. Here we review evidence indicating that C factors and regulators are locally synthesized in the peripheral nerve and we discuss the evidence supporting the protective or detrimental role of C activation in health, injury and disease of the peripheral nerve.     

Role of tumor‐associated macrophages in human malignancies: friend or foe?

Tumor‐associated macrophages (TAMs) play a pivotal role in tumor growth in human malignancies. Published studies have analyzed the relationship between TAM infiltration and the prognosis of patients for many human tumors. Most studies reported a positive correlation between TAM density and a poor prognosis. Studies focusing on macrophage phenotypes emphasized the protumor role of M2 anti‐inflammatory macrophages in many types of human tumors. However, TAMs influence tumor progression in various ways that depend on differences in tumor sites, histology, and microenvironments. In this review, we summarize the function of TAMs in various human malignancies by reviewing the data provided in studies of TAMs in human malignancies.     

Helminth infection in populations undergoing epidemiological transition: a friend or foe?

Helminth infections are highly prevalent in developing countries, especially in rural areas. With gradual development, there is a transition from living conditions that are dominated by infection, poor sanitation, manual labor, and traditional diet to a situation where burden of infections is reduced, infrastructure is improved, sedentary lifestyle dominates, and processed food forms a large proportion of the calorie intake. The combinations of some of the changes in lifestyle and environment are expected to result in alteration of the landscape of diseases, which will become dominated by non-communicable disorders. Here we review how the major helminth infections affect a large proportion of the population in the developing world and discuss their impact on the immune system and the consequences of this for other infections which are co-endemic in the same areas. Furthermore, we address the issue of decreasing helminth infections in many parts of the world within the context of increasing inflammatory, metabolic, and cardiovascular diseases.     

Phosphorylcholine: friend or foe of the immune system?

Phosphorylcholine (PC) is a structural component of a variety of prokaryotic and eukaryotic pathogens. In some cases, PC in infectious agents can benefit the infected host due to its targeting by both the innate and adaptive immune responses. However, as discussed here, PC exhibits a surprising range of immunomodulatory properties that might be to the detriment of the host.     

Toll-like receptor 3 in viral pathogenesis: friend or foe?

Viral infections frequently induce acute and chronic inflammatory diseases, yet the contribution of the innate immune response to a detrimental host response remains poorly understood. In virus‐infected cells, double‐stranded RNA (dsRNA) is generated as an intermediate during viral replication. Cell necrosis (and the release of endogenous dsRNA) is a common event during both sterile and infectious inflammatory processes. The discovery of Toll‐like receptor 3 (TLR3) as an interferon‐inducing dsRNA sensor led to the assumption that TLR3 was the master sentinel against viral infections. This simplistic view has been challenged by the discovery of at least three members of the DExd/H‐box helicase cytosolic sensors of dsRNA that share with TLR3 the Toll–interleukin‐1 receptor (TIR) ‐adapter molecule TIR domain‐containing adaptor protein interferon‐β (TRIF) for downstream type I interferon signalling. Data are conflicting on the role of TLR3 in protective immunity against viruses in the mouse model. Varying susceptibility to infection and disease outcomes have been reported in TLR3‐immunodeficient mice. Surprisingly, the susceptibility to develop herpes simplex virus‐1 encephalitis in humans with inborn defects of the TLR3 pathway varies, and TLR3‐deficient humans do not show increased susceptibility to other viral infections. Therefore, a current challenge is to understand the protective versus pathogenic contribution of TLR3 in viral infections. We review recent advances in the identification of TLR3‐signalling pathways, endogenous and virus‐induced negative regulators of the TLR3 cascade, and discuss the protective versus pathogenic role of TLR3 in viral pathogenesis.     

Host immune response in B-cell lymphomas: friend or foe?

The interaction of B-cell malignancies with the host immune system is a dynamic and bilateral process. Certain lymphomas more commonly arise within a background of autoimmunity or chronic infection. Initiation of these tumors is commonly reliant on antigenic stimulation and/or T-cell help. Apart from its tumor-fueling role, the host immune response plays a critical role in cancer immunosurveillance and immunoediting. The concept of immunoediting holds that the immune system sculpts the tumor's immunogenicity in a dynamic process that involves three essential phases: elimination, equilibrium, and escape. Data obtained by studying gene-targeted animals and human lymphomas that support the critical role of the immune response in the initiation, progression, and immunoediting of lymphoid malignancies are summarized here. A thorough understanding of this interaction will lead to the identification of more rational treatment targets and improved immunotherapies in B-cell lymphomas.     

IL-17A in hepatitis B infection: friend or foe?

Hepatitis B virus (HBV) is one of the most prevalent and infectious agents that leads to liver disease in humans. Five clinical forms of HBV infection exist, including fulminant, acute, chronic, asymptomatic and occult. The chronic, asymptomatic and occult forms are long-term infections that can lead to hepatocellular carcinoma (HCC) and liver cirrhosis. The mechanisms responsible for progression of these forms of the infection to HCC and liver cirrhosis are not yet clearly understood or characterised. However, genetic and immunological parameters may play important roles in the disease. IL-17A is an important cytokine involved in early immune responses against fungal and bacterial infections, but its role in the response against viral infections is yet to be fully clarified. The crucial roles of IL-17A in the pathogenesis of autoimmune and destructive immune-related diseases have been documented and may provide insights into its functions during hepatitis infection. Therefore, the aim of this review was to address the recent information regarding the status and association of IL-17A during hepatitis B infection and its related disorders, including HCC and liver cirrhosis.     

T helper type 1 cells in asthma: friend or foe?

A large body of research supports a pathogenic role for T helper 2 cells in asthma, although T helper 1 cell-type responses may also contribute. Using the principle of T helper cell cross-regulation, investigators have attempted to regulate the pathological effects of T helper 2 cells using regimens that may promote T helper 1 cell-type inflammation. In this review, we propose that the use of factors that promote T helper 1 cell differentiation and activation to treat asthma may be counterproductive, and that alternate regulatory approaches should be explored.     

Role of interleukin-21 in HBV infection: friend or foe?

Interleukin (IL)-21, a cytokine produced by activated CD4⁺ T cells, has broad pleiotropic actions that affect the functions of a variety of lymphoid cells. The roles of IL-21 in modulating immunity to infections are currently being defined. Notably, IL-21-mediated cellular and humoral immune responses play an important role in determining the outcome of viral infection. This article reviews the current knowledge on the critical role of IL-21 in hepatitis B virus (HBV) infection. As a competent intermediary, IL-21 derived from virus-specific CD4⁺ T cells plays key roles in sustaining CD8⁺ T cells and promoting B-cell responses that are essential for effective viral control. However, as a mediator of inflammation, IL-21 is also involved in the development of HBV-induced liver cirrhosis and exacerbating liver injury. Overall, the current data point to IL-21 as an immunomodulatory cytokine in HBV infection. Immunotherapeutic strategies aimed at optimizing the beneficial effects of IL-21 in HBV infection may prove to be a rigorous challenge in the future, as they should foster the strengths of IL-21 while circumventing potential drawbacks.     

The role of microRNAs in respiratory viral infection: friend or foe?

MicroRNAs (miRNAs) have emerged as a class of regulatory RNAs in host–pathogen interactions. Aberrant miRNA expression seems to play a central role in the pathology of several respiratory viruses, promoting development and progression of infection. miRNAs may thus serve as therapeutic and prognostic factors for respiratory viral infectious disease caused by a variety of agents. We present a comprehensive review of recent findings related to the role of miRNAs in different respiratory viral infections and discuss possible therapeutic opportunities aiming to attenuate the burden of viral infections. Our review supports the emerging concept that cellular and viral‐encoded miRNAs might be broadly implicated in human respiratory viral infections, with either positive or negative effects on virus life cycle. Copyright © 2016 John Wiley & Sons, Ltd.     

Withholding iron as a cellular defence mechanism – friend or foe?

During infection one critical host defence strategy is an attempt to withhold iron from invading pathogens. This is achieved by by proinflammatory cytokines such as IL-6 inducing hepcidin. The net result of this is the removal of iron from the circulation and its sequestration within cells, including cells of the immune system such as macrophages. As macrophages are central cells for controlling infections with intracellular bacteria such as Salmonella and Mycobacteria, modulation of iron by hepcidin can lead to the provision of an ideal cellular iron source for these pathogens. Here we discuss how activation of macrophages with IFN-gamma not only up-regulates antimicrobial effector mechanisms but also modulates iron regulatory proteins such as ferroportin to reduce intracellular iron availability.     

Induction of innate immune responses in the female genital tract: friend or foe of HIV-1 infection?

Heterosexual transmission of HIV-1 and HSV-2 across the genital tract epithelial tissue is one of the primary routes for dissemination of these viral infections. Mucosal innate immunity is the first line of defense against invading pathogens. A vast majority of mucosal HIV-1 exposures do not result in productive infections which may indicate that the innate mucosal immune system is highly protective. It has been shown that Toll-like receptors (TLR)-induced innate antiviral immunity in the genital mucosa lead to induction of type I and III interferon and prevention of HSV-2 infection. The innate antiviral function of type I and III interferons and other innate factors at genital mucosa against HIV-1 is not well defined. In this review, we summarize our current understanding and advances of the innate mucosal response to genital viral infections, including HIV-1 and HSV-2, focusing on those factors that may prevent or accelerate initial infection. Understanding how each of these components contributes to mucosal innate antiviral immunity may lead to the development of novel and effective strategies to use microbicides or antiviral agents to control HIV-1 acquisition and/or transmission.     

Detection of anti-HLA antibodies by solid-phase assay in kidney transplantation: friend or foe?

Pre-formed and de novo anti-human leukocyte antigen (HLA) antibodies induce antibody-mediated rejection and are also involved in mechanisms leading to chronic graft nephropathy. The detection of anti-HLA antibodies by solid-phase assay (SPA) has revolutionized the management of immunized patients before and after kidney transplantation. Characterized by high sensitivity and specificity, the clinical relevance of anti-HLA antibodies by SPA has to be clarified. The presence of donor-specific antibody at the epitope level, their titer, and the use of different crossmatch technologies could help to determine which of the anti-HLA antibodies are friends and which are foes in kidney transplantation. In this review, we summarize the current state of the art on this debated topic, and give clinical guidelines for the management of antibody detection pre- and post-transplantation, based on these evidences and our own clinical expertise.     

Is 8860 variation a rare polymorphism or associated as a secondary effect in HCM disease?

Introduction

mtDNA defects, both deletions and point mutations, have been associated with hypertrophic cardiomyopathies. The aim of this study was to establish a spectrum for mtDNA mutations in Iranian hypertrophic cardiomyopathy (HCM) patients.

Material and methods

The control group was chosen among the special medical centre visitors who did not have hypertrophic cardiomyopathy or any related heart disease. Hypertrophic cardiomyopathy (HCM) is widely accepted as a pluricausal or multifactorial disease. Because of the linkage between energy metabolism in the mitochondria and cardiac muscle contraction, it is reasonable to assume that mitochondrial abnormalities may be responsible for some forms of HCM. Point mutations and deletions in the two hot spot regions of mtDNA were investigated by PCR and sequencing methods.

Results

Some unreported point mutations have been found in this study but no deletion was detected. Meanwhile some of these point mutations have been investigated among HCM patients for the first time.

Conclusions

A8860G transition was detected in a high proportion, raising the question whether this rare polymorphism is associated as a secondary effect in HCM disease.