"On the one hand, it can directly destroy pathogens that have been taken up by phagocytes. "NO has two very different effects during an infection," Müller said. major was not mainly a result of NO killing the pathogen directly, which occurs only during the peak of the immune response, but rather the indirect effect of NO reducing the availability of proliferation-permissive host cells throughout the infection. The results showed that reduced proliferation of L. major and hence do not generate iNOS activity.īy combining mathematical modeling with in vivo observation of the infected mice by intravital 2-photon fluorescent protein biosensors, the scientists were able to track the growth rate and viability of the pathogens over the course of infection using the data on pathogen viability and proliferation obtained from the intravital 2-photon microscopy to test and refine the predictions of mathematical models the team had constructed of how the immune system works. The researchers employed both normal mice and Rag1−/− mice, which are devoid of an adaptive immune response against L. major under low-dose and high-dose conditions to determine how NO affects both the physiology of the parasite and the inflammatory environment of the infection site. Leishmaniasis, which has so far proved difficult to treat, is spread by the bite of phlebotomine sand flies and is endemic to the tropics, subtropics, and southern Europe.
In the study, the researchers, led by Andreas Müller, PhD, of the Institute of Molecular and Clinical Immunology at the University Medical Center Magdeburg in Germany, set out to understand more precisely the direct and indirect mechanisms by which NO combats intracellular parasites, which are microparasites that can grow and reproduce inside the cells of a host.Īs a target, the research team chose Leishmania major, an intracellular protozoan parasite that causes the tropical disease leishmaniasis.
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