Role of PAFR-MHC-II-CD38 interactions in infections

Abstract

Abstract Infectious diseases are the most prevalent cause of deaths around the world. Chronic contagious ailments will account for seven out of ten deaths in the world by 2020. The most significant problem in the treatment of the infectious disease is the ever-increasing rate of resistance to drugs mounted by pathogens. Our preliminary results suggest that during antigen presentation the major histocompatibility complex II (MHC-II) engages two associate protein molecules CD38 and Platelet Activating Factor Receptor (PAFR). CD38 and PAFR elicit two counteractive signaling pathways in APCs resulting in the release of either proinflammatory cytokine such as IL-12 or anti-inflammatory cytokines such as IL-10 respectively. Pathogens show remarkable adaptability to the drugs by either metabolizing the drug molecules or by changing the surface profile to neutralize binding of drugs to the pathogens. Therefore, there is a requirement to find new treatment modalities that do not target the pathogens but aid the immune system to eliminate the pathogens. Our preliminary data further suggest that the use of associate molecule during antigen presentation decides the fate of pathogens such as Salmonella Typhimurium or Staphylococcus aureus in macrophages. For example, if MHC-II engages CD38 to signal inside the macrophages leading to reduced pathogen survival in macrophages and mice, while MHC-II-signaling via PAFR aid the pathogen survival in macrophages and mice. Our studies also suggest that combinatorial use of PAFR inhibitor (WEB2086) and antibiotics ampicillin reduced the growth of S. Typhimurium or S. aureus in macrophages and mice.