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TLR 9 involvement in early protection induced by immunization with rPb27 against Paracoccidioidomycosis
Elis Araujo Morais1, Daniela Ferreira Chame1, Eliza Mathias Melo1
1Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, Belo Horizonte, Brazil.
Abstract:
Paracoccidioidomycosis is caused by fungi of the Paracoccidioides genus and constitutes the most prevalent deep mycosis in Latin America. Toll-like receptors promote immune response against infectious agents. Recently, it was reported that TLR9 is crucial for mice survival during the first 48 h of P. brasiliensis infection. In this study, we used CPG oligodeoxynucleotide motif as an adjuvant with and without rPb27 to immunize mice against Paracoccidioidomycosis. CPG adjuvant induced differential recruitment of lymphocytes in the inflammatory process and a lower recruitment of neutrophils. In addition, CPG induced the production of pro-inflammatory cytokines such as IL-1β, TNF-α, IL-6 and IL-12; increased phagocytic ability and microbicidal activity by macrophages; and induced differential production of lgG2a and lgG2b, subtypes of Ig. Knockout mice for TLR9 and IL-12 showed higher fungal loads and rates of mortality compared to control mice after 30 days of infection. The association between CPG and rPb27 induced a high level of protection against Paracoccidioidomycosis after the first 30 days of infection but not at 60 days. Our findings demonstrate that TLR 9 plays a role in the protection induced by immunization with rPb27 and confirms the importance of TLR9 in the initial protection against Paracoccidioidomycosis.
Insights
Toll-like receptor 9 (TLR9) is vital for initial protection against Paracoccidioidomycosis. Immunization with CPG adjuvant and rPb27 enhances immune responses, improving survival in mice during the early stages of infection.
Area of Science:
- Immunology
- Mycology
- Infectious Diseases
Background:
- Paracoccidioidomycosis, a deep fungal infection endemic to Latin America, is caused by Paracoccidioides fungi.
- Toll-like receptors (TLRs) are critical for initiating immune responses against pathogens.
- TLR9 has been identified as essential for early survival in mice infected with Paracoccidioides brasiliensis.
Purpose of the Study:
- To investigate the role of TLR9 in protection against Paracoccidioidomycosis.
- To evaluate the efficacy of CPG oligodeoxynucleotide (adjuvant) combined with rPb27 for immunization.
Main Methods:
- Mice were immunized with CPG adjuvant, with or without rPb27, and subsequently infected with Paracoccidioides brasiliensis.
- Immune cell recruitment, cytokine production, macrophage activity, and antibody subtypes were analyzed.
- TLR9 and IL-12 knockout mice were used to assess their role in infection outcomes.
Main Results:
- CPG adjuvant modulated lymphocyte and neutrophil recruitment, increased pro-inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-12), and enhanced macrophage microbicidal activity.
- Mice immunized with CPG and rPb27 showed significant protection against Paracoccidioidomycosis up to 30 days post-infection.
- TLR9 and IL-12 knockout mice exhibited increased fungal loads and mortality rates.
Conclusions:
- TLR9 is crucial for the protective immune response induced by rPb27 immunization against Paracoccidioidomycosis.
- The study highlights TLR9's importance in the initial phase of protection against this deep fungal infection.
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