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Naïve CD8 T cell IFNγ responses to a vacuolar antigen are regulated by an inflammasome-independent NLRP3 pathway and Toxoplasma gondii ROP5.

Publication ,  Journal Article
Kongsomboonvech, AK; Rodriguez, F; Diep, AL; Justice, BM; Castallanos, BE; Camejo, A; Mukhopadhyay, D; Taylor, GA; Yamamoto, M; Saeij, JPJ ...
Published in: PLoS Pathog
August 2020

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.

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Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

August 2020

Volume

16

Issue

8

Start / End Page

e1008327

Location

United States

Related Subject Headings

  • Virulence
  • Virology
  • Vacuoles
  • Toxoplasmosis, Animal
  • Toxoplasma
  • Signal Transduction
  • Protozoan Proteins
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Mice
  • Macrophages
 

Citation

APA
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Kongsomboonvech, A. K., Rodriguez, F., Diep, A. L., Justice, B. M., Castallanos, B. E., Camejo, A., … Jensen, K. D. C. (2020). Naïve CD8 T cell IFNγ responses to a vacuolar antigen are regulated by an inflammasome-independent NLRP3 pathway and Toxoplasma gondii ROP5. PLoS Pathog, 16(8), e1008327. https://doi.org/10.1371/journal.ppat.1008327
Kongsomboonvech, Angel K., Felipe Rodriguez, Anh L. Diep, Brandon M. Justice, Brayan E. Castallanos, Ana Camejo, Debanjan Mukhopadhyay, et al. “Naïve CD8 T cell IFNγ responses to a vacuolar antigen are regulated by an inflammasome-independent NLRP3 pathway and Toxoplasma gondii ROP5.PLoS Pathog 16, no. 8 (August 2020): e1008327. https://doi.org/10.1371/journal.ppat.1008327.
Kongsomboonvech AK, Rodriguez F, Diep AL, Justice BM, Castallanos BE, Camejo A, et al. Naïve CD8 T cell IFNγ responses to a vacuolar antigen are regulated by an inflammasome-independent NLRP3 pathway and Toxoplasma gondii ROP5. PLoS Pathog. 2020 Aug;16(8):e1008327.
Kongsomboonvech, Angel K., et al. “Naïve CD8 T cell IFNγ responses to a vacuolar antigen are regulated by an inflammasome-independent NLRP3 pathway and Toxoplasma gondii ROP5.PLoS Pathog, vol. 16, no. 8, Aug. 2020, p. e1008327. Pubmed, doi:10.1371/journal.ppat.1008327.
Kongsomboonvech AK, Rodriguez F, Diep AL, Justice BM, Castallanos BE, Camejo A, Mukhopadhyay D, Taylor GA, Yamamoto M, Saeij JPJ, Reese ML, Jensen KDC. Naïve CD8 T cell IFNγ responses to a vacuolar antigen are regulated by an inflammasome-independent NLRP3 pathway and Toxoplasma gondii ROP5. PLoS Pathog. 2020 Aug;16(8):e1008327.

Published In

PLoS Pathog

DOI

EISSN

1553-7374

Publication Date

August 2020

Volume

16

Issue

8

Start / End Page

e1008327

Location

United States

Related Subject Headings

  • Virulence
  • Virology
  • Vacuoles
  • Toxoplasmosis, Animal
  • Toxoplasma
  • Signal Transduction
  • Protozoan Proteins
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Mice
  • Macrophages