Murine C3 of the complement system affects infection by Leptospira interrogans

Leptospirosis is an infectious neglected disease estimated to affect more than one million people worldwide each year. The Complement System plays a vital role in eliminating infectious agents. However, its precise role in leptospirosis remains to be fully understood. We investigated the importance of C3 in L. interrogans serovar Kennewicki strain Pomona Fromm (LPF) infection. Lack of C3 leads to decreased leukocyte number, impaired inflammatory response and failure to eliminate bacteria during the early stages of infection, which may cause interstitial nephritis later. These findings could be explained, at least in part, by the lower presence of local opsonins. Furthermore, antibody production against Leptospira was compromised in the absence of C3, highlighting the importance of CR2 in B lymphocyte proliferation and the adjuvant role of C3d in humoral immunity. Leptospires can be eliminated through the urine, and according to our study, the lack of C3 delays the elimination of LPF through urine during the early stages of the infection. These results strongly suggest the crucial role of C3 protein in orchestrating an appropriate inflammatory response against LPF infection and in effectively eliminating the bacteria from the body during the acute phase of leptospirosis.