{"doi":"10.1371/journal.ppat.1008327","title":"Naïve CD8 T cell IFNγ responses to a vacuolar antigen are regulated by an inflammasome-independent NLRP3 pathway and Toxoplasma gondii ROP5","abstract":"Host resistance to Toxoplasma gondii relies on CD8 T cell IFNγ responses, which if modulated by the host or parasite could influence chronic infection and parasite transmission between hosts. Since host-parasite interactions that govern this response are not fully elucidated, we investigated requirements for eliciting naïve CD8 T cell IFNγ responses to a vacuolar resident antigen of T. gondii, TGD057. Naïve TGD057 antigen-specific CD8 T cells (T57) were isolated from transnuclear mice and responded to parasite-infected bone marrow-derived macrophages (BMDMs) in an antigen-dependent manner, first by producing IL-2 and then IFNγ. T57 IFNγ responses to TGD057 were independent of the parasite's protein export machinery ASP5 and MYR1. Instead, host immunity pathways downstream of the regulatory Immunity-Related GTPases (IRG), including partial dependence on Guanylate-Binding Proteins, are required. Multiple T. gondii ROP5 isoforms and allele types, including 'avirulent' ROP5A from clade A and D parasite strains, were able to suppress CD8 T cell IFNγ responses to parasite-infected BMDMs. Phenotypic variance between clades B, C, D, F, and A strains suggest T57 IFNγ differentiation occurs independently of parasite virulence or any known IRG-ROP5 interaction. Consistent with this, removal of ROP5 is not enough to elicit maximal CD8 T cell IFNγ production to parasite-infected cells. Instead, macrophage expression of the pathogen sensors, NLRP3 and to a large extent NLRP1, were absolute requirements. Other members of the conventional inflammasome cascade are only partially required, as revealed by decreased but not abrogated T57 IFNγ responses to parasite-infected ASC, caspase-1/11, and gasdermin D deficient cells. Moreover, IFNγ production was only partially reduced in the absence of IL-12, IL-18 or IL-1R signaling. In summary, T. gondii effectors and host machinery that modulate parasitophorous vacuolar membranes, as well as NLR-dependent but inflammasome-independent pathways, determine the full commitment of CD8 T cells IFNγ responses to a vacuolar antigen.","journal":"PLoS Pathogens","year":2020,"id":69269,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9444,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":331962,"name":"Felipe Rodriguez","orcid":"0000-0001-7217-4817","position":1,"is_corresponding":false},{"id":366964,"name":"Anh L. Diep","orcid":"0000-0003-0217-324X","position":2,"is_corresponding":false},{"id":366965,"name":"Brandon M. Justice","orcid":"0000-0003-1197-1171","position":3,"is_corresponding":false},{"id":368074,"name":"Brayan E. Castallanos","orcid":null,"position":4,"is_corresponding":false},{"id":368075,"name":"Ana Camejo","orcid":null,"position":5,"is_corresponding":false},{"id":287519,"name":"Debanjan Mukhopadhyay","orcid":"0000-0002-8921-4106","position":6,"is_corresponding":false},{"id":282433,"name":"Gregory A. Taylor","orcid":"0000-0003-1966-0917","position":7,"is_corresponding":false},{"id":366966,"name":"Masahiro Yamamoto","orcid":"0000-0002-6821-2785","position":8,"is_corresponding":false},{"id":236240,"name":"Jeroen P. J. Saeij","orcid":"0000-0003-0289-7109","position":9,"is_corresponding":false},{"id":241387,"name":"Michael L. Reese","orcid":"0000-0001-9401-9594","position":10,"is_corresponding":false},{"id":280690,"name":"Kirk D.C. Jensen","orcid":"0000-0003-0707-964X","position":11,"is_corresponding":false},{"id":366963,"name":"Angel K. Kongsomboonvech","orcid":"0000-0002-2599-131X","position":0,"is_corresponding":true}],"reference_count":158,"raw_metadata":null,"created_at":"2026-07-18T21:42:22.705573Z","pmid":"32853276","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}