ArticleInfection and immunity2010
Toll-like receptor 4 signaling leads to severe fungal infection associated with enhanced proinflammatory immunity and impaired expansion of regulatory T cells.
Article in Infection and immunity, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 101 citations in OpenAlex.
- Extracellular vesicles from virulentVirulence · 2024Article
- Analysis and Interpretation of Automated Blood Count in the Treatment of Chronic Paracoccidioidomycosis.Journal of fungi (Basel, Switzerland) · 2024Article
- MDSCs use a complex molecular network to suppress T-cell immunity in a pulmonary model of fungal infection.Frontiers in cellular and infection microbiology · 2024Article
- The immunosuppressive activity of myeloid-derived suppressor cells in murine Paracoccidioidomycosis relies on Indoleamine 2,3-dioxygenase activity and Dectin-1 and TLRs signaling.Scientific reports · 2023Article
- Proteomic analysis reveals changes in the proteome of human THP-1 macrophages infected withFrontiers in cellular and infection microbiology · 2023Article
- Myeloid-derived suppressor cells are associated with impaired Th1 and Th17 responses and severe pulmonary paracoccidioidomycosis which is reversed by anti-Gr1 therapy.Frontiers in immunology · 2023Article
- Exploring SARS-CoV2 host-pathogen interactions and associated fungal infections cross-talk: Screening of targets and understanding pathogenesis.Computational and structural biotechnology journal · 2022Article
- AhR Ligands Modulate the Differentiation of Innate Lymphoid Cells and T Helper Cell Subsets That Control the Severity of a Pulmonary Fungal Infection.Frontiers in immunology · 2021Article
- NLRP3 Inflammasome Contributes to Host Defense AgainstFrontiers in immunology · 2021Article
- Effects ofFrontiers in veterinary science · 2021Article
- β2 Integrin-Mediated Susceptibility toFrontiers in cellular and infection microbiology · 2021Article
- Molecular insights into the mechanisms of susceptibility of Labeo rohita against oomycete Aphanomyces invadans.Scientific reports · 2020Article
- IKKγ/NEMO Is Required to Confer Antimicrobial Innate Immune Responses in the Yellow Mealworm,International journal of molecular sciences · 2020Article
- Integrating GWAS with bulk and single-cell RNA-sequencing reveals a role for LY86 in the anti-Candida host response.PLoS pathogens · 2020Article
- Intracellular PRRs Activation in Targeting the Immune Response Against Fungal Infections.Frontiers in cellular and infection microbiology · 2020Review
- Regulatory T cells in paracoccidioidomycosis.Virulence · 2019Review
- Long-term ex vivo haematopoietic-stem-cell expansion allows nonconditioned transplantation.Nature · 2019Article
- Innate and adaptive immune responses to fungi in the airway.The Journal of allergy and clinical immunology · 2018Review
- The Syk-Coupled C-Type Lectin Receptors Dectin-2 and Dectin-3 Are Involved inFrontiers in immunology · 2018Article
- TLR3 Is a Negative Regulator of Immune Responses AgainstFrontiers in cellular and infection microbiology · 2018Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Toll-like receptors (TLRs) present in innate immune cells recognize pathogen molecular patterns and influence immunity to control the host-parasite interaction. The objective of this study was to characterize the involvement of TLR4 in the innate and adaptive immunity to Paracoccidioides brasiliensis, the most important primary fungal pathogen of Latin America. We compared the responses of C3H/HeJ mice, which are naturally defective in TLR4 signaling, with those of C3H/HePas mice, which express functional receptors, after in vitro and in vivo infection with P. brasiliensis. Unexpectedly, we verified that TLR4-defective macrophages infected in vitro with P. brasiliensis presented decreased fungal loads associated with impaired synthesis of nitric oxide, interleukin-12 (IL-12), and macrophage chemotactic protein 1 (MCP-1). After intratracheal infection with 1 million yeasts, TLR4-defective mice developed reduced fungal burdens and decreased levels of pulmonary nitric oxide, proinflammatory cytokines, and antibodies. TLR4-competent mice produced elevated levels of IL-12 and tumor necrosis factor alpha (TNF-alpha), besides cytokines of the Th17 pattern, indicating a proinflammatory role for TLR4 signaling. The more severe infection of TLR4-normal mice resulted in increased influx of activated macrophages and T cells to the lungs and progressive control of fungal burdens but impaired expansion of regulatory T cells (Treg cells). In contrast, TLR4-defective mice were not able to clear their diminished fungal burdens totally, a defect associated with deficient activation of T-cell immunity and enhanced development of Treg cells. These divergent patterns of immunity, however, resulted in equivalent mortality rates, indicating that control of elevated fungal growth mediated by vigorous inflammatory reactions is as deleterious to the hosts as low fungal loads inefficiently controlled by limited inflammatory reactions.
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