Pathogenesis and Treatment of Cytokine Storm Induced by Infectious Diseases.

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.

Interleukin-17 mediates lung injury by promoting neutrophil accumulation during the development of contagious caprine pleuropneumonia.

Contagious caprine pleuropneumonia (CCPP) is a highly contagious infectious disease of goats caused by Mycoplasma capricolum subspecies capripneumoniae (Mccp). CCPP outbreaks usually result in high morbidity and mortality of the affected goats, making this disease a major cause of economic losses to goat producers globally. However, the pathogenesis of CCPP remains unclear. Here, we show that IL-17-driven neutrophil accumulation is involved in the lung damage in CCPP goats. During CCPP development, intense inflammatory infiltrates could be observed in the injured lungs. Specifically, neutrophils were observed to be present within the alveoli. Increased IL-17 release drove the excessive influx of neutrophils into the lung, as IL-17 effectively stimulated the production of neutrophil chemoattractants from lung epithelial cells following Mccp infection. Our data highlight a critical role of IL-17-driven neutrophil accumulation in the pathogenesis of CCPP and suggest that IL-17 may potentially be a useful immunotherapeutic target for the treatment of CCPP.

Methods for Enhancing Clustered Regularly Interspaced Short Palindromic Repeats/Cas9-Mediated Homology-Directed Repair Efficiency.

The evolution of organisms has provided a variety of mechanisms to maintain the integrity of its genome, but as damage occurs, DNA damage repair pathways are necessary to resolve errors. Among them, the DNA double-strand break repair pathway is highly conserved in eukaryotes, including mammals. Nonhomologous DNA end joining and homologous directed repair are two major DNA repair pathways that are synergistic or antagonistic. Clustered regularly interspaced short palindromic repeats genome editing techniques based on the nonhomologous DNA end joining repair pathway have been used to generate highly efficient insertions or deletions of variable-sized genes but are error-prone and inaccurate. By combining the homology-directed repair pathway with clustered regularly interspaced short palindromic repeats cleavage, more precise genome editing via insertion or deletion of the desired fragment can be performed. However, homologous directed repair is not efficient and needs further improvement. Here, we describe several ways to improve the efficiency of homologous directed repair by regulating the cell cycle, expressing key proteins involved in homologous recombination and selecting appropriate donor DNA.

Pathogenicity of blood orf virus isolates in the development of dairy goat contagious pustular dermatitis.

Contagious pustular dermatitis is an exanthematous zoonotic disease caused by the orf virus. Pandemic outbreaks of this disease cause great economic losses, while the pathogenesis of this disease still remains obscure. In this study, blood samples were collected from 628 asymptomatic goats across China for PCR-based virus detection. We detected the orf virus in the blood of asymptomatic goats. Moreover, the orf virus obtained from the blood of infected goats was infectious and induced typical symptoms of contagious pustular dermatitis after inoculation of uninfected dairy goats. In summary, our data provide evidence that asymptomatic animals may be carriers of orf virus. Our findings should contribute to elucidating the details underlying the pathogenesis of contagious pustular dermatitis.