ArticlePLoS pathogens2012
The CTLA-4 and PD-1/PD-L1 inhibitory pathways independently regulate host resistance to Plasmodium-induced acute immune pathology.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
What it found
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Who cites it
77 citing papers in PubMed, 114 citations in OpenAlex.
- Controlled Human Malaria Infection (CHMI) differentially affects cell-mediated and antibody responses to CSP and AMA1 induced by adenovirus vaccines with and without DNA-priming.Human vaccines & immunotherapeutics · 2015Trial
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- Advanced immunotherapy across diseases and the role of artificial intelligence: A review.Biomolecules & biomedicine · 2026Review
- Ligature-induced periodontitis in mice potentially accelerates CD4Frontiers in immunology · 2026Article
- Parasitic Infections and Carcinogenesis: Molecular Mechanisms, Immune Modulation, and Emerging Therapeutic Strategies.Oncology research · 2026Review
- Combined anti-PD-1 and amphotericin B therapy reduces fungal burden and enhances control of murine paracoccidioidomycosis.Frontiers in cellular and infection microbiology · 2026Article
- Impact of co-infection with Plasmodium berghei ANKA in Leishmania major-parasitized mice on immune modulation and cutaneous leishmaniasis.PLoS neglected tropical diseases · 2025Article
- Synergistic blockade of TIGIT and PD-L1 increases type-1 inflammation and improves parasite control during murine blood-stageInfection and immunity · 2024Article
- Blocking the CTLA-4 and PD-1 pathways during pulmonary paracoccidioidomycosis improves immunity, reduces disease severity, and increases the survival of infected mice.Frontiers in immunology · 2024Article
- Increased Neutrophil Percentage and Neutrophil-T Cell Ratio Precedes Clinical Onset of Experimental Cerebral Malaria.International journal of molecular sciences · 2023Article
- SARS-CoV-2 decreases malaria severity in co-infected rodent models.Frontiers in cellular and infection microbiology · 2023Article
- Vaccination with anFrontiers in immunology · 2023Article
- Drug Development Strategies for Malaria: With the Hope for New Antimalarial Drug Discovery-An Update.Advances in medicine · 2023Review
- Activation of cGAS-STING by Lethal Malaria N67C Dictates Immunity and Mortality through Induction of CD11bAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Deciphering the Plasmodium falciparum malaria-specific CD4+ T-cell response: ex vivo detection of high frequencies of PD-1+TIGIT+ EXP1-specific CD4+ T cells using a novel HLA-DR11-restricted MHC class II tetramer.Clinical and experimental immunology · 2022Article
- Molecular profiling reveals features of clinical immunity and immunosuppression in asymptomatic P. falciparum malaria.Molecular systems biology · 2022Article
- In vitro characterization of a small molecule PD-1 inhibitor that targets the PD-l/PD-L1 interaction.Scientific reports · 2022Article
- Mannose inhibitsFrontiers in immunology · 2022Article
- Memory CD8Immunology · 2021Article
- Immune Evasion ofPathogens (Basel, Switzerland) · 2021Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 3 countries.
Funding
Abstract
The balance between pro-inflammatory and regulatory immune responses in determining optimal T cell activation is vital for the successful resolution of microbial infections. This balance is maintained in part by the negative regulators of T cell activation, CTLA-4 and PD-1/PD-L, which dampen effector responses during chronic infections. However, their role in acute infections, such as malaria, remains less clear. In this study, we determined the contribution of CTLA-4 and PD-1/PD-L to the regulation of T cell responses during Plasmodium berghei ANKA (PbA)-induced experimental cerebral malaria (ECM) in susceptible (C57BL/6) and resistant (BALB/c) mice. We found that the expression of CTLA-4 and PD-1 on T cells correlates with the extent of pro-inflammatory responses induced during PbA infection, being higher in C57BL/6 than in BALB/c mice. Thus, ECM develops despite high levels of expression of these inhibitory receptors. However, antibody-mediated blockade of either the CTLA-4 or PD-1/PD-L1, but not the PD-1/PD-L2, pathways during PbA-infection in ECM-resistant BALB/c mice resulted in higher levels of T cell activation, enhanced IFN-γ production, increased intravascular arrest of both parasitised erythrocytes and CD8(+) T cells to the brain, and augmented incidence of ECM. Thus, in ECM-resistant BALB/c mice, CTLA-4 and PD-1/PD-L1 represent essential, independent and non-redundant pathways for maintaining T cell homeostasis during a virulent malaria infection. Moreover, neutralisation of IFN-γ or depletion of CD8(+) T cells during PbA infection was shown to reverse the pathologic effects of regulatory pathway blockade, highlighting that the aetiology of ECM in the BALB/c mice is similar to that in C57BL/6 mice. In summary, our results underscore the differential and complex regulation that governs immune responses to malaria parasites.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.