Current Immunology Reviews (Discontinued) - Volume 15, Issue 2, 2019

The mucosal surfaces and the skin are the primary sites of interactions between the mammalian host and the external environment. These sites are exposed continuously to the diverse components of the environment, including subcellular, unicellular and multicellular organisms, dietary agents and food products; and numerous other soluble or cellular air or water borne products. The development of innate and adaptive immunity in the mucosal surfaces and the skin are the principal mechanism of mammalian defense evolved to date, in order to maintain effective homeostatic balance between the host and the external environment. The innate immune functions are mediated by a number of host specific Pathogen Recognition Receptors (PRR), designed to recognize unique Pathogen Associated Molecular Patterns (PAMP), essential to the molecular structure of the microorganism. The major components of specific adaptive immunity in the mucosal surfaces include the organized antigen-reactive lymphoid follicles in different inductive mucosal sites and the effector sites of the lamina propria and sub-epithelial regions, which contain lymphoid and plasma cells, derived by the homing of antigen sensitized cells from the inductive sites. The acquisition of environmental microbiome by the neonate in its mucosal surfaces and the skin, which begins before or immediately after birth, has been shown to play a critical and complex role in the development of mucosal immunity. This report provides an overview of the mammalian microbiome and highlights its role in the evolution and functional development of immunologic defenses in the mucosal surface under normal physiologic conditions and during infectious and non-infectious inflammatory pathologic states associated with altered microbiota.

After the outbreak in French Polynesia, Zika virus (ZIKV) explosive pandemic occurred in 2015, reports that ZIKV was linked to other diseases, especially neurological complications such as Guillain-Barré Syndrome (GBS), also burst in almost every continent, thereby turning into an international concern. In South America, the highest incidence occurred in Venezuela with approximately 680 cases of GBS after ZIKV infection. Currently, the main roots of this association remain unknown. In this regard, it is thought that the immune system plays a central role in such association through the host protection or even improving ZIKV establishment and progression. Nonneutralizing auto-antibodies, the complement system, self-reactive T cells, inflammation, the “cytokine storm”, prior exposures to other arboviruses such as dengue virus and chikungunya virus, the age and genetic susceptibility of the patient, and the biology of the vector are the main determinant factors, which perhaps, are involved in the pathological relationship: ZIKV and GBS. On the other hand, more multidisciplinary studies are required to provide means to develop effective therapeutics against this new global health threat that represents an emerging danger that can increase again and trigger other neurological disorders.

Macrophages are the phagocytic sentinel cells of our body, with high plasticity required to maintain homeostasis. This incredibly diverse set of cells, in response to various environmental stimuli such as cytokines and other factors, constantly alters their functional state/phenotype. They undergo polarization not only into conventional M1/M2 axis but also undergo a diverse spectrum of macrophage subtypes which play critical roles in various immune functions and homeostasis. In the tumor microenvironment, monocytes polarize along with the alternatively activated macrophages AAM or M2 macrophages associated with pro-tumoral features whereas M1 macrophages exert antitumor functions. Tumor-Associated Macrophage (TAM) infiltration has long been associated with poor prognosis and therefore represents potential diagnostic and prognostic biomarkers in solid tumors. Inhibiting the recruitment of monocytes into the tumor microenvironment and targeted deletion of TAMs have shown promising results. Targeting the TAMs towards M1-like macrophages has also demonstrated to be an efficient way to prevent tumor progression and metastasis. Here in this article, we review how TAMs orchestrate different steps in tumor progression and metastasis and the opportunities to target them in the quest for cancer prevention and treatment. Further, we explore how chemotherapies and immunotherapies can target TAM reprogramming and depletion to serve as a strategy for the control of various types of cancers in the future.

Cancer is the second leading cause of death and morbidity in the world among noncommunicable diseases after cardiovascular ailments. With the advancement in science and research, a number of therapies have been developed to treat cancer, including chemotherapy, radiotherapy and immunotherapy. Chemo and radiotherapy have been in use since the last two decades, however these are not devoid of their own intrinsic problems, such as myelotoxicity, cardiotoxicity, nephrotoxicity, neurotoxicity and immunosuppression. Hence, there is an urgent need to develop alternative methods for the treatment of cancer. An increase in the cases of various cancers has encouraged the researchers to discover novel, more effective drugs from plant sources. In this review, fifteen medicinal plants alongside their products with anticancer effects will be introduced and discussed, as well as the most important plant compounds responsible for the anticancer activity of the plant. Several phenolic and alkaloid compounds have been demonstrated to have anticancer effects on various types of cancers. The most fundamental and efficient role exhibited by these secondary plant metabolites against cancer involves removing free radicals and antioxidant effects, induction of apoptosis, cell cycle arrest and inhibition of angiogenesis. Moreover, recent studies have shown that plants and their metabolites may provide an alternative to the existing approaches, including chemotherapies and radiotherapies, in the treatment of cancer. In this review, a brief overview of important secondary metabolites having anticancer activity will be given, along with the major molecular mechanisms involved in the disease. In addition to this, recent advances in secondary metabolites from various medicinal plants in the prevention and treatment of cancer will be explored.

Recent research has highlighted the growing public health concern arising from mismanagement of malarial and non-malarial febrile illnesses that present with similar clinical symptoms. A retrospective examination of patient records suggests that a syndrome-based diagnosis results in over-diagnosis of malaria. Consequently, interventions to mitigate the frequency of presumptive treatment of fever in malaria-endemic settings have been sought, especially for resourcelimited areas. Guidelines that promote the use of microbiological tests and modern diagnostic kits have demonstrated laudable progress in the ongoing challenge of febrile illness management. However, this has brought attention to other factors like the complication of mixed infections. These issues, which remain significant limitations to current tools and methods in the accurate diagnosis and subsequent therapy of febrile illnesses, call for innovative diagnostic interventions. Advancements in biomedical research over the last decade have led to the introduction of state-of-the-art molecular techniques of omics origin that provide the possibility of diverse applications in disease diagnostics. Here, we present notable challenges in febrile illness management, describe currently available tools and methods for diagnosis, and discuss the opportunities for future progress, including harnessing cuttingedge transcriptional profiling and proteomics technology to detect host immunological signatures during infection.

Background: Preterm Birth (PTB) is one of the main causes of neonatal death and infant mortality and morbidity. The pro-inflammatory cytokine interleukin-6 (IL-6) is a major proinflammatory mediator of the host response to infection and malondialdehyde (MDA) is a marker of oxidative stress. Objective: To evaluate potential associations between IL-6 and MDA levels in women with preterm birth. Methods: A total of 150 women (66 with full-term and 84 with PTB) were enrolled in this case-control study. Predesigned performas were filled through questionnaire interviews to collect data on personal, demographic, occupational, lifestyle and reproductive history. Blood samples were collected within 36 hours of delivery. Serum concentrations of IL-6 and MDA were determined in mothers with full-term and preterm birth. Results: The mean age was marginally higher; whereas BMI was slightly lower in cases (PTB) as compared to controls (full-term) subjects. Serum IL-6 and MDA levels were significantly higher in subjects with PTB than full-term birth. The data were further analyzed with respect to underweight, normal and overweight/obese BMI. In all the BMI categories, the levels of IL-6 and MDA were higher in PTB cases. Among the PTB categories, the levels of IL-6 and MDA were highest in moderate to late preterm birth. A significant positive correlation was found between IL-6 and MDA levels. There was a weak negative correlation between either IL-6 or MDA and the number of gestational weeks. Conclusion: Elevated maternal serum levels of Interleukin-6 and Malondialdehyde in preterm as compared to full-term birth might suggest that inflammation and oxidative stress play a critical role in PTB.