Suppressed expression of miR-378 targeting gzmb in N cells is required to control dengue virus infection

Dengue virus （DENV） remains a major public health threat because no vaccine or drugs are available for the prevention and treatment of DENV infection, and the immunopathogenesis mechanisms of DENV infection are not fully understood. Cytotoxic molecules, such as granzyme B （GrzB）, may be necessary to control viral infections. However, the exact role of GrzB during DENV infection and the mechanisms regulating GrzB expression during DENV infection are not clear. This study found that miR-27a~, miR-3Oe, and miR-378 were down-regulated in DENV-infected patients, and DENV infection in humans induced a significant up-regulation of GrzB in natural killer （NK） cells and CD8＋ T cells. Further investigation indicated that NK cells, but not CD8＋ T cells, were the major sources of GrzB, and miR-378, but not miR-27a~ or miR-3Oe, suppressed GrzB expression in NK cells. Notably, we found that overexpression of miR-378 using a miR-378 agomir in DENV-infected mice inhibited GrzB expression and promoted DENV replication. These results suggest the critical importance of miR-378 in the regulation of GrzB expression and a protective role for GrzB in controlling DENV replication in vivo. Therefore, this study provides a new insight into the immunopathogenesis mechanism of DENV infection and a biological basis for the development of new therapeutic strategies to control DENV infection.

Th1 cytokines, true functional signatures for protective immunity against TB?

The lack of an effective preventative vaccine against tuberculosis(TB)presents a great challenge to TB control.Since it takes an extremely long time to accurately determine the protective efficacy of TB vaccines,there is a great need to identify the surrogate signatures of protection to facilitate vaccine development.Unfortunately,antigen-specific Th1 cytokines that are currently used to evaluate the protective efficacy of the TB vaccine,do not align with the protection and failure of TB vaccine candidates in clinical trials.In this review,we discuss the limitation of current Th1 cytokines as surrogates of protection and address the potential elements that should be considered to finalize the true functional signatures of protective immunity against TB.

Nutrition Metabolism and Infections

Infection and nutrition are intricately interacted and further influence human health.Infections are a worldwide health problem and malnutrition plays a significant role in the emergence of infection.Growing evidence suggests that the optimization of dietary nutrients intake is crucial in maintaining systemic immunity and may help improve resistance to infections.In this review,we explore a wide range of topics including interactions between nutrients and various infectious diseases.We also discuss the role of diet-induced gut microbiota in the infection-nutrition cycle and review how dietary-microbiome crosstalk may affect disease development and progression,which may provide an attractive option to the design of a diet leading to favorable outcomes in the future.We will also present evidence and propose mechanisms of nutrients that may specifically modulate host immunity and metabolism to infectious pathogens and also cover its influence on nutrition,focusing on immuno-nutrients.We provide representative nutrients in the present review based on their intensive studies and wide acceptance of their immuno-modulating properties.Moreover,the efficacy and translational cost of their plausible utility to be anti-infective nutrients are also reviewed.Finally,we highlight the current progress and challenges to gain a better understanding of the research into microbiota,infectious diseases,and nutrition with an emphasis on future research directions.

Non-coding RNA: a key regulator of the pathogenicity and immunity of Flaviviridae viruses infection

Flaviviridae is a family of viruses that mainly spread through arthropod vectors,such as mosquitoes.Major members of the Flaviviridae family include dengue virus(DENV),yellow fever virus,Zika virus(ZIKV),West Nile virus and hepatitis C virus(HCV).As Flaviviridae viruses remain a major global public health threat,elucidation of the exact mechanisms of pathogenesis during infection is required for the successful control of these deadly viruses.

Neutrophils, reverse traffic and detrimental potential

Transmigration of leukocytes through venular walls into the inflamed tissues plays a central role in innate immune res- ponses against infection or injury. Trans- endothelial migration （TEM） was widely believed to be the final step in the process of leukocyte emigration into inflamed tissues. Leukocyte TEM is driven by large-scale, comlicated molecular interactions that allow leukocyte TEM to occur with minimal disruption to the complex and delicate structures of vessel walls.1,2 However, the molecu- lar mechanisms underlying the leukocyte