Murine C3 of the complement system affects infection by Leptospira interrogans
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Published on: August 14, 2021
Julia Avian Vassalakis1, Denise Harumi Silva Yamashita1, Leonardo Moura Midon1
1Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, SP, Brazil.
Abstract:
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.
Insights
The complement system protein C3 is crucial for fighting Leptospira infection. Its absence impairs the immune response, delays bacterial clearance, and hinders antibody production, impacting acute leptospirosis.
Area of Science:
- Immunology
- Infectious Diseases
- Microbiology
Background:
- Leptospirosis is a neglected infectious disease affecting over a million people annually.
- The complement system is vital for pathogen elimination, but its role in leptospirosis is not fully understood.
- Complement component 3 (C3) is a key player in innate and adaptive immunity.
Purpose of the Study:
- To investigate the role of C3 in Leptospira interrogans serovar Kennewicki strain Pomona Fromm (LPF) infection.
- To understand how C3 influences the host's immune response and bacterial clearance.
- To explore C3's impact on antibody production and bacterial shedding.
Main Methods:
- Utilized a mouse model lacking the C3 gene.
- Infected C3-deficient and wild-type mice with LPF.
- Assessed immune cell populations, inflammatory markers, bacterial load, and antibody responses.
- Monitored bacterial shedding in urine.
Main Results:
- C3 deficiency resulted in reduced leukocyte numbers and impaired inflammatory responses.
- Lack of C3 led to a failure in early bacterial elimination and delayed urinary clearance of LPF.
- Antibody production against Leptospira was compromised in C3-deficient mice.
- Lower levels of local opsonins were observed in the absence of C3.
Conclusions:
- C3 protein is essential for orchestrating an effective inflammatory response against LPF infection.
- C3 plays a critical role in the early elimination of Leptospira during the acute phase.
- The complement system, particularly C3, is vital for controlling leptospirosis and preventing long-term complications like interstitial nephritis.
