Differences in the M1 and M2 Macrophage Subtypes between the Sexes Determine Susceptibility to Francisella tularensis Infection
Francisella tularensis is the causative agent of the human disease tularemia. It is highly infectious with as few as 10 microorganisms via inhalation causing a lethal infection. F. tularensis infects a variety of cell types, including macrophages and neutrophils, since it needs to enter, survive and proliferate in order to cause pathogenicity. Disease is the result of over activating the host’s own inflammatory response initiated by the macrophage’s response to infection. Known differences exist in the intensity of the inflammatory response between the sexes which leads to differences in sensitivity to autoimmune and infectious disease. Males tend to be more susceptible to infectious diseases whereas females tend to be more susceptible to autoimmune diseases. In contrast, our preliminary data demonstrated that female mice were more susceptible than male mice to the infectious disease F. tularensis. We hypothesized that female macrophages respond to F. tularensis infection by generating a more intense inflammatory response which makes females more susceptible to F. tularensis disease. We determined the relative ratio of M1/M2 subtypes in vivo and their subsequent response to F. tularensis infection in vivo and ex vivo. Splenic macrophages were isolated and differentiated in vitro into M1 and M2 subtypes in order to directly compare differences in the intracellular response between males and females in response to F. tularensis infection. Our results demonstrated that females possess a higher abundance of M1 macrophages and that these M1 macrophages are more inflammatory in response to F. tularensis infection.
Sanchez, Michelle A, "Differences in the M1 and M2 Macrophage Subtypes between the Sexes Determine Susceptibility to Francisella tularensis Infection" (2019). ETD Collection for University of Texas, El Paso. AAI27671526.