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Peptidorhamnomannan negatively modulates the immune response in a scedosporiosis murine model
Mariana I D S Xisto1, Livia Cristina Liporagi-Lopes2, Julián Esteban Muñoz3
1Departamento de Microbiologia Geral, Instituto de Microbiologia Paulo de Góes, Universidade Federal do Rio de Janeiro (UFRJ), Rio de Janeiro, Brazil.
Abstract:
In this study, we analyzed the impact of immunization with the peptidorhamnomannan (PRM) from the cell wall of the fungus Scedosporium (Lomentospora) prolificans in a murine model of invasive scedosporiosis. Immunization with PRM decreased the survival of mice infected with S. prolificans. Immunization of mice with PRM led to decreased secretion of pro-inflammatory cytokines and chemokines but did not affect the secretion of IL-10. Mice immunized with PRM showed an increase in IgG1 secretion, which is an immunoglobulin linked to a nonprotective response. Splenocytes isolated from mice infected with S. prolificans and immunized with PRM showed no differences in the percentages of Th17 cells and no increase in the frequency of the CD4(+)CD62L(Low) T cell population. PRM-immunized mice showed a significant increase in the percentage of Treg cells. In summary, our results indicated that immunization with PRM did not assist or improve the immunological response against S. prolificans infection. PRM exacerbated the infection process by reducing the inflammatory response, thereby facilitating colonization, virulence and dissemination by the fungus.
Insights
Immunization with peptidorhamnomannan (PRM) from Scedosporium prolificans worsened invasive scedosporiosis in mice. PRM reduced protective immune responses, increasing fungal virulence and dissemination.
Area of Science:
- Mycology
- Immunology
- Infectious Diseases
Background:
- Scedosporium (Lomentospora) prolificans causes invasive infections, particularly in immunocompromised individuals.
- The fungal cell wall component, peptidorhamnomannan (PRM), is a potential target for antifungal therapies.
- Understanding the host immune response to PRM is crucial for developing effective treatments.
Purpose of the Study:
- To evaluate the impact of PRM immunization on the host immune response and survival in a murine model of invasive scedosporiosis.
- To investigate the effects of PRM immunization on cytokine and chemokine secretion, immunoglobulin production, and T cell populations.
Main Methods:
- Murine model of invasive scedosporiosis induced by S. prolificans infection.
- Immunization with purified PRM prior to fungal challenge.
- Analysis of survival rates, serum cytokine and chemokine levels, immunoglobulin G1 (IgG1) production, and T cell populations (Th17, CD4(+)CD62L(Low), Treg) in splenocytes.
Main Results:
- PRM immunization significantly decreased survival rates in infected mice.
- Immunization led to reduced pro-inflammatory cytokine and chemokine secretion, while IL-10 levels remained unaffected.
- Increased IgG1 secretion, indicative of a non-protective immune response, was observed.
- No significant changes in Th17 or CD4(+)CD62L(Low) T cell populations were detected, but an increase in regulatory T cells (Treg) was noted.
Conclusions:
- PRM immunization does not enhance the immunological response against S. prolificans infection.
- PRM immunization exacerbates scedosporiosis by dampening the inflammatory response, promoting fungal colonization, virulence, and dissemination.
