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Immune response to the Rhodococcus equi infection in high and low antibody-producing mice (Selection IV-A)
Sílvia C B Pedrini1, Michele J Acorci, João G G Pinto
1Department of Microbiology and Immunology of the Biosciences Institute, UNESP, São Paulo State University, Botucatu, Brazil.
Abstract:
Rhodococcus equi is a gram-positive, facultative intracellular bacterium which infects macrophages and causes rhodococcal pneumonia and enteritis in foals. Recently, this agent has been recognized as an opportunistic pathogen for immunocompromised humans. Several murine experimental models have been used to study R. equi infection. High (H(IV-A)) and Low (L(IV-A)) antibody (Ab)-producers mice were obtained by bi-directional genetic selections for their ability to produce antibodies against sheep and human erythrocytes (Selection IV-A). These lines maintain their phenotypes of high and low responders also for other antigens than those of selection (multispecific effect). A higher macrophage activity in L(IV-A) mice has been described for several intracellular infectious agents, which could be responsible for their intense macrophage antigens (Ag)-handling and low Ab production. Due to these differences, L(IV-A) mice were found to exhibit a better performance to trigger an effective immune response towards intracellular pathogens. The objective of this work was to characterize the immune response of Selection IV-A against R. equi. H(IV-A) and L(IV-A) mice were infected with 2.0x10(6) CFU of ATCC 33701+R. equi by intravenous route. With regards to bacterial clearance and survival assays, L(IV-A) mice were more resistant than H(IV-A) mice to virulent R. equi. L(IV-A) mice presented a higher hydrogen peroxide (H2O2) and nitric oxide (NO) endogenous production by splenic macrophages than H(IV-A) mice. L(IV-A) expressed the most intense cellular response, available by the Delayed-Type Hypersensitivity (DTH) reaction, which activated macrophages and produced more H2O2 and NO. The three times higher specific antibodies titres in H(IV-A) indicated that Selection IV-A maintained the multispecific effect and the polygenic control of humoral and cellular responses also to R. equi.
Insights
Low antibody-producing mice (L(IV-A)) showed greater resistance to Rhodococcus equi infection due to enhanced macrophage activity and nitric oxide production. High antibody-producing mice (H(IV-A)) maintained higher antibody titers, demonstrating distinct immune response profiles.
Area of Science:
- Immunology
- Microbiology
- Genetics
Background:
- Rhodococcus equi is a gram-positive bacterium causing pneumonia in foals and opportunistic infections in immunocompromised humans.
- Murine models are crucial for studying R. equi, with distinct antibody (Ab)-producing lines (High IV-A and Low IV-A) selected for multispecific antibody responses.
- Low Ab-producing mice (L(IV-A)) exhibit heightened macrophage activity, suggesting a potential role in controlling intracellular pathogens.
Purpose of the Study:
- To characterize the immune response of genetically selected High (H(IV-A)) and Low (L(IV-A)) antibody-producing mice against Rhodococcus equi infection.
- To evaluate bacterial clearance, survival rates, and macrophage function in response to R. equi challenge.
Main Methods:
- H(IV-A) and L(IV-A) mice were infected intravenously with R. equi (ATCC 33701).
- Bacterial clearance, survival assays, and splenic macrophage production of hydrogen peroxide (H2O2) and nitric oxide (NO) were assessed.
- Delayed-Type Hypersensitivity (DTH) reactions were measured to evaluate cellular immune response.
Main Results:
- L(IV-A) mice demonstrated significantly better resistance to R. equi infection, with improved bacterial clearance and survival compared to H(IV-A) mice.
- Splenic macrophages from L(IV-A) mice exhibited higher endogenous production of H2O2 and NO.
- L(IV-A) mice showed a more intense DTH cellular response, correlating with enhanced macrophage activation and mediator production.
- H(IV-A) mice produced three times higher specific antibody titers, confirming the maintenance of the multispecific antibody production phenotype.
Conclusions:
- Genetic selection for antibody production influences immune response to R. equi, with L(IV-A) mice exhibiting superior control of infection via enhanced macrophage-mediated immunity.
- The study confirms the multispecific nature of the antibody response and the polygenic control of both humoral and cellular immunity in the selected mouse lines.
- These findings highlight the potential of L(IV-A) mice as a model for studying host resistance mechanisms against intracellular bacterial pathogens like R. equi.
