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Vassalakis JA. The role of Complement System component C3 during in vivo infection by Leptospira interrogans. [Masters thesis (Immunology)]. São Paulo: Instituto de Ciências Biomédicas, Universidade de São Paulo; 2017. The Complement System is part of the innate immune response and is of paramount importance for the elimination of infectious diseases and to guarantee homeostasis. Leptospirosis is a zoonosis caused by bacteria of the genus Leptospira. These bacteria invade the body through the injured skin or mucous membranes after direct or indirect contact with the urine of rodents, invading the bloodstream until reach organs such as liver, lung, spleen and kidney. In this work, we investigated the importance of the Complement protein C3 in the in vivo infection by L. interrogans. C57BL/6 mice deficient in C3 protein (B6.C3) and, as control, congenic mice (B6.C3) infected with Leptospira interrogans serovar Kennewicki strain Pomona Fromm (LPF) were used. We observed that deficiency of C3 protein causes a failure of the immune response, causing a decrease in the cellular proliferation of monocytes, neutrophils, B lymphocytes, T CD4 and T CD8 lymphocytes in the spleen. This failure of cell proliferation results in a decrease in the inflammatory response, making it difficult to eliminate the bacteria from the main target organs (liver, kidney, lung and spleen) in the first days of infection. The decrease in cell proliferation in the spleen of the B6.C3 mice could be observed in the peripheral circulation, where no significant number was found on the third day of infection as observed in the wild type mice, increasing only on the sixth day of infection. Although the C3deficient mice had a lower LPF elimination capacity on the initial days of infection, mice were able to eliminate the LPF from their target organs on the sixth day, although they still had higher numbers of bacteria when compared to the wild type animals. This failure of elimination of bacterial load has been shown to have consequences in later stages of the disease, especially in the kidney, where we observed the appearance of interstitial nephritis only in C3-deficient mice. In the histopathological analysis, we observed that the C3 protein triggered an intense inflammatory process in the liver, developing necrosis and larger areas of leukocyte infiltrates, seen in a lower intensity in C3 deficient mice. The elimination of leptospiras can occur through the urine of the hosts. Our data showed that the mice eliminate the bacteria by the urine in the later phase of the infection after six days and that the C3-deficient mice have a larger number of LPF being eliminated than the wild type mice at that time of the infection. Our work has been able to demonstrate that C3 protein, especially in the early days of infection, is important in assembling an appropriate inflammatory response to fight LPF infection and eliminate the bacteria in the body.

O papel do componente C3 do sistema complemento na infecção <i>in vivo</i> por <i>Leptospira interrogans</i>.