The mammalian intestine is colonized by over a trillion microbes that comprise the “gut microbiota,” a microbial community which has co-evolved with the host to form a mutually beneficial relationship. Accumulating evidence indicates that the gut microbiota participates in immune system maturation and also plays a central role in host defense against pathogens. Here we review some of the mechanisms employed by the gut microbiota to boost the innate immune response against pathogens present on epithelial mucosal surfaces. Antimicrobial peptide secretion, inflammasome activation and induction of host IL-22, IL-17, and IL-10 production are the most commonly observed strategies employed by the gut microbiota for host anti-pathogen defense. Taken together, the body of evidence suggests that the host gut microbiota can elicit innate immunity against pathogens.

The intestinal tract of vertebrates is normally colonized with a remarkable number of commensal microorganisms that are collectively referred to as gut microbiota. Gut microbiota has been demonstrated to interact with immune cells and to modulate specific signaling pathways involving both innate and adaptive immune processes. Accumulated evidence suggests that the imbalance of Th17 and Treg cells is associated with the development of many diseases. Herein, we emphatically present recent findings to show how specific gut microbiota organisms and metabolites shape the balance of Th17 and Treg cells. We also discuss the therapeutic potential of fecal microbiota transplantation (FMT) in diseases caused by the imbalance of Th17 and Treg cells

Viral infections cause substantial human morbidity and mortality, and are a significant health burden worldwide. Following a viral infection, the host may initiate complex antiviral immune responses to antagonize viral invasion and replication. However, proinflammatory antiviral immune responses pose a great threat to the host if not properly held in check. Interleukin (IL)-17 is a pleiotropic cytokine participating in a variety of physiological and pathophysiological conditions, including tissue integrity maintenance, cancer progression, autoimmune disease development and, more intriguingly, infectious diseases. Abundant evidence suggests that while IL-17 plays a crucial role in enhancing effective antiviral immune responses, it may also promote and exacerbate virus-induced illnesses. Accumulated experimental and clinical evidence has broadened our understanding of the seemingly paradoxical role of IL-17 in viral infections and suggests that IL-17-targeted immunotherapy may be a promising therapeutic option. Herein, we summarize current knowledge regarding the protective and pathogenic roles of IL-17 in viral infections, with emphasis on underlying mechanisms. The various and critical roles of IL-17 in viral infections necessitate the development of therapeutic strategies that are uniquely tailored to both the infectious agent and the infection environment.

Cytokine storm is a phenomenon characterized by strong elevated circulating cytokines that most often occur after an overreactive immune system is activated by an acute systemic infection. A variety of cells participate in cytokine storm induction and progression, with profiles of cytokines released during cytokine storm varying from disease to disease. This review focuses on pathophysiological mechanisms underlying cytokine storm induction and progression induced by pathogenic invasive infectious diseases. Strategies for targeted treatment of various types of infection-induced cytokine storms are described from both host and pathogen perspectives. In summary, current studies indicate that cytokine storm-targeted therapies can effectively alleviate tissue damage while promoting the clearance of invading pathogens. Based on this premise, “multi-omics” immune system profiling should facilitate the development of more effective therapeutic strategies to alleviate cytokine storms caused by various diseases.

Background: Gut microbiota play important roles in their co-evolution with mammals. However, little is understood about gut bacterial community of Tibetan sheep compared with other sheep breeds. In this study, we investigated the gut bacterial community in 4 different sheep breeds living in the Qinghai-Tibetan Plateau (QTP) of China using high-throughput sequencing (HTS) technique. Results: The results suggested that bacterial community abundance and breeds diversity of Tibetan sheep (TS) were significantly lower than that of the other three breeds of sheep [Dorset sheep (DrS), Dorper sheep (DrS) and Small Tail Han sheep (STHS)] (p < 0.05). Principal coordinates analysis (PCoA) and nonmetric multidimensional scaling (NMDS) analysis indicated that microbiome composition of TS was significantly different from that of other three sheep breeds (p < 0.01). Firmicutes was the most predominant microbial phylum in the gut, followed by Bacteroidetes. The gut bacterial community of TS showed higher proportions of phylum Spirochaetes, Proteobacteria and Verrucomicrobia, compared to the other three sheep breeds, but the Deferribacteres was absent in TS. At the genus level, Treponema, Succinivibrio, 5-7 N15 and Prevotella showed significantly higher abundance in TS than in the other three sheep breeds (p < 0.05). Conclusions: In this study, we first employed HTS to understand the gut microbiomes among different sheep breeds in QTP of China.

Primary biliary cholangitis (PBC), an autoimmune liver disease occurring predominantly in women, is characterized by high titers of serum anti-mitochondrial antibodies (AMAs) and progressive intrahepatic cholestasis. The immune system plays a critical role in PBC pathogenesis and a variety of immune cell subsets have been shown to infiltrate the portal tract areas of patients with PBC. Amongst the participating immune cells, CD4 T cells are important cytokine-producing cells that foster an inflammatory microenvironment. Specifically, these cells orchestrate activation of other immune cells, including autoreactive effector CD8 T cells that cause biliary epithelial cell (BEC) injury and B cells that produce large quantities of AMAs. Meanwhile, other immune cells, including dendritic cells (DCs), natural killer (NK) cells, NKT cells, monocytes, and macrophages are also important in PBC pathogenesis. Activation of these cells initiates and perpetuates bile duct damage in PBC patients, leading to intrahepatic cholestasis, hepatic damage, liver fibrosis, and eventually cirrhosis or even liver failure. Taken together, the body of accumulated clinical and experimental evidence has enhanced our understanding of the immunopathogenesis of PBC and suggests that immunotherapy may be a promising treatment option. Herein, we summarize current knowledge regarding immunological abnormalities of PBC patients, with emphasis on underlying pathogenic mechanisms. The differential immune response which occurs over decades of disease activity suggests that different therapies may be needed at different stages of disease.