Influenza virus infection is a serious threat to humans and animals, with the potential to cause severe pneumonia and death. Annual vaccination strategies are a mainstay to prevent complications related to influenza. However, protection from the emerging subtypes of influenza A viruses (IAV) even in vaccinated individuals is challenging. Innate immune cells are the first cells to respond to IAV infection in the respiratory tract. Virus replication-induced production of cytokines from airway epithelium recruits innate immune cells to the site of infection. These leukocytes, namely, neutrophils, monocytes, macrophages, dendritic cells, eosinophils, natural killer cells, innate lymphoid cells, andγδT cells, become activated in response to IAV, to contain the virus and protect the airway epithelium while triggering the adaptive arm of the immune system. This review addresses different anti-influenza virus schemes of innate immune cells and how these cells fine-tune the balance between immunoprotection and immunopathology during IAV infection. Detailed understanding on how these innate responders execute anti-influenza activity will help to identify novel therapeutic targets to halt IAV replication and associated immunopathology.

Cellular stress response activates a complex program of an adaptive response called integrated stress response (ISR) that can allow a cell to survive in the presence of stressors. ISR reprograms gene expression to increase the transcription and translation of stress response genes while repressing the translation of most proteins to reduce the metabolic burden. In some cases, ISR activation can lead to the assembly of a cytoplasmic membraneless compartment called stress granules (SGs). ISR and SGs can inhibit apoptosis, pyroptosis, and necroptosis, suggesting that they guard against uncontrolled regulated cell death (RCD) to promote organismal homeostasis. However, ISR and SGs also allow cancer cells to survive in stressful environments, including hypoxia and during chemotherapy. Therefore, there is a great need to understand the molecular mechanism of the crosstalk between ISR and RCD. This is an active area of research and is expected to be relevant to a range of human diseases. In this review, we provided an overview of the interplay between different cellular stress responses and RCD pathways and their modulation in health and disease.

Introduction: Wound infections are significant group of infections in the hospitals worldwide. The wide spread uses of antimicrobial agents lead to emergence of resistant pathogens contributing to increased morbidity and mortality. Accurate and prompt antimicrobial therapy is required to reduce the complications. This study was aimed to investigate pyogenic bacterial pathogens and their susceptibility patterns. Methods: A cross sectional study was carried out at Gandaki Medical College Teaching Hospital from July to December 2018. Wound specimens obtained from adult patients were inoculated onto appropriate media and pathogens were identified using standard microbiological methods. Antimicrobial susceptibility patterns were determined by Kirby-Bauer disc diffusion method following the guidelines of Clinical and Laboratory Standard Institute (CLSI). Results: A total of 264 specimens were included in the study of which 167 (63.3%) were positive for bacterial growth. Of these, polymicrobial growth was observed in two specimens. Gram positive bacteria (119, 70.4%) were the leading cause of infections, Staphylococcus aureus (102, 85.7%) being the most dominant. Among the Gram negative pathogens (50, 29.6%), Escherichia coli (31,62%) was found to be the predominant followed by Pseudomonas aeurogenosa (10, 20%). Overall, the isolates were resistance to Ampicillin (90.7%), Amoxycillin (64.9%), Cloxacillin (68%), Ofloxacin (61.5%) and Cotrimoxazole (55.6%). Lesser rates of resistance were observed to Doxycycline, Erythromycin, Amikacin, Gentamicin and Imipenem. Conclusion: This study revealed the most common pathogens causing pyogenic wound infections in our setting. Again, these pathogens are resistance to commonly used antibiotics. Therefore, this study could be helpful to develop proper guidelines of antibiotics to be used for prophylactic and empiric treatment.

Stress granules (SGs) are cytoplasmic membraneless compartments that can form in stressed cells. There is an intricate relationship between SGs and innate immune signaling pathways. A previous study reported that the innate immune signaling mediated by Toll-like receptors (TLRs) can inhibit SGs induced by endoplasmic reticulum stress (ER stress) in bone-marrow-derived macrophages (BMDMs) and the chemotherapy drug oxaliplatin in B16 melanoma cells. We wanted to test if this observation can be generalized to other cell types. First, we recapitulated the results from the previous study showing TLR signaling-mediated inhibition of SGs in BMDMs induced by ER stress. However, SGs formed in response to ER stress were either not inhibited or only very weakly inhibited by TLR4 stimulation in human lung cancer-derived A549 cells, murine immortalized mouse lung fibroblasts (iMLFs) and primary murine mouse lung fibroblasts. This correlated with a weak induction of IKK complex kinase activity by TLR4 stimulation in these cells. SGs formed by sodium arsenite treatment also remained unaffected by TLR4 signaling. Our results indicate that the innate immune signaling-mediated inhibition of SGs is cell-type-dependent, thus opening a new avenue for mechanistic studies of the crosstalk between innate immune and stress signaling pathways.