Mechanisms of mucosal immunity at the female reproductive tract involved in defense against HIV infection.

Human immunodeficiency virus-1 remains a major global health threat. Since the virus is often transmitted through sexual intercourse and women account for the majority of new infections within the most endemic regions, research on mucosal immunity at the female reproductive tract (FRT) is of paramount importance. At the FRT, there are intrinsic barriers to HIV-1 infection, such as epithelial cells and the microbiome, and immune cells of both the innate and adaptive arms are prepared to respond in case the virus overcomes the first line of defense. In this review, we discuss recent findings on FRT mucosal mechanisms of HIV-1 defense and highlight research gaps. While defense from HIV-1 infection at the FRT has been understudied, current and future research is essential to develop new therapeutics and vaccines that can protect this unique mucosal site from HIV-1.

Acute pericardial postischemic inflammatory responses: Characterization using a preclinical porcine model.

BACKGROUND: Pericardial fluid (PF) contains cells, proteins, and inflammatory mediators, such as cytokines, chemokines, growth factors, and matrix metalloproteinases. To date, we lack an adequate understanding of the inflammatory response that acute injury elicits in the pericardial space. OBJECTIVE: To characterize the inflammatory profile in the pericardial space acutely after ischemia/reperfusion. METHODS: Pigs were used to establish a percutaneous ischemia/reperfusion injury model. PF was removed from pigs at different time points postanesthesia or postischemia/reperfusion. Flow cytometry was used to characterize the immune cell composition of PF, while multiplex analysis was performed on the acellular portion of PF to determine the concentration of inflammatory mediators. There was a minimum of 3 pigs per group. RESULTS: While native PF mainly comprises macrophages, we show that neutrophils are the predominant inflammatory cell type in the pericardial space after injury. The combination of acute ischemia/reperfusion (IR) and repeatedly accessing the pericardial space significantly increases the concentration of interleukin-1 beta (IL-1ß) and interleukin-1 receptor antagonist (IL-1ra). IR significantly increases the pericardial concentration of TGFß1 but not TGFß2. We observed that repeated manipulation of the pericardial space can also drive a robust pro-inflammatory response, resulting in a significant increase in immune cells and the accumulation of potent inflammatory mediators in the pericardial space. CONCLUSION: In the present study, we show that both IR and surgical manipulation can drive robust inflammatory processes in the pericardial space, consisting of an increase in inflammatory cytokines and alteration in the number and composition of immune cells.