Evidence map›Paper›PMID 42386736›Full record

ArticleNature communications2026

Dual activation of NLRP3 and pyrin inflammasomes mediates host responses to the human fungal pathogen Coccidioides.

Ka Pui Sharon Yau, Jonathan Rodrigo Erlich, Priscila Rodriguez, Sara McArdle, Cameron J Nowell, Matthew M Tate, Janset Onyuru, Ahalya Ratnavel, Aanika Desai, Jane Symington and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Ka Pui Sharon YauDivision of Allergy, Immunology, and Rheumatology, Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
Jonathan Rodrigo ErlichDivision of Allergy, Immunology, and Rheumatology, Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-0343-3990
Priscila RodriguezDivision of Allergy, Immunology, and Rheumatology, Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
Sara McArdleMicroscopy and Histology Core Facility, La Jolla Institute for Immunology, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-3795-3772
Cameron J NowellMonash Institute of Pharmaceutical Sciences, Melbourne, VIC, Australia.ORCID http://orcid.org/0000-0002-8662-9840
Matthew M TateVeterans Affairs San Diego Healthcare System, San Diego, CA, USA.ORCID http://orcid.org/0000-0002-8544-887X
Janset OnyuruDivision of Allergy, Immunology, and Rheumatology, Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
Ahalya RatnavelDivision of Allergy, Immunology, and Rheumatology, Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
Aanika DesaiDivision of Allergy, Immunology, and Rheumatology, Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
Jane SymingtonDepartment of Pediatrics, University of California, San Francisco, San Francisco, CA, USA.
Guillaume CastillonDepartment of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-0657-1683
Zbigniew MikulskiMicroscopy and Histology Core Facility, La Jolla Institute for Immunology, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-1918-9216
Simon GoldsteinMicroscopy and Histology Core Facility, La Jolla Institute for Immunology, La Jolla, CA, USA.ORCID http://orcid.org/0009-0008-1259-4017
Aaron F CarlinDivision of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-1669-8066
Joshua FiererVeterans Affairs San Diego Healthcare System, San Diego, CA, USA.
Theo N KirklandDivision of Infectious Diseases and Global Public Health, Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
Hal M Hoffman *Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA.
Sinem Beyhan *Veterans Affairs San Diego Healthcare System, San Diego, CA, USA. sbeyhan@health.ucsd.edu.ORCID http://orcid.org/0000-0003-0906-7538
Ben A Croker *Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, University of California, San Diego, La Jolla, CA, USA. bcroker@health.ucsd.edu.ORCID http://orcid.org/0000-0002-0885-3599

Funding

Innate immune mechanisms of the host response to CoccidioidesU19AI166059 · NIAID · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Joshua Fierer · 2022 to 2026
$10.0M
NIAID NIH HHS U19 AI166059U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID) U19AI166059
6 · The paper itself

Abstract

Coccidioides is a dimorphic fungal pathogen that grows as a mold in soil and produces infectious arthroconidia. Inhaled arthroconidia transition to spherules containing endospores in mammalian hosts. How distinct developmental forms of Coccidioides interact with immune cells remains poorly defined. Here, we show that arthroconidia activates TLR2 and induces NLRP3-pyrin inflammasomes in macrophages, while ferroptotic signaling promotes arthroconidia killing. Upon transition to spherules, only ruptured spherules-not intact ones-trigger IL-1β production through NLRP3-pyrin inflammasomes and GSDMD-GSDME pores. A TLR2-NLRP3-pyrin-IL-18 axis in macrophages promotes spherule growth. Endospores activate NLRP3 but not pyrin inflammasomes. Caspase-1-deficient mice show improved disease tolerance to coccidioidomycosis despite equivalent fungal burdens, correlating with enhanced neutrophil extracellular trap formation in lung granulomas. Neutrophils respond to spherules through NLRP3-pyrin inflammasomes, GSDMD-GSDME, and MLKL. Together, these findings reveal that Coccidioides morphotypes elicit distinct yet overlapping immune programs, coordinating inflammasome activation and regulated cell death to shape host-pathogen dynamics.

Indexed as

CoccidioidesCoccidioidomycosisInflammasomesNLR Family, Pyrin Domain-Containing 3 ProteinAnimalsCaspase 1GasderminsHost-Pathogen InteractionsHumansInterleukin-18Interleukin-1betaIntracellular Signaling Peptides and ProteinsMacrophagesMiceMice, Inbred C57BLMice, KnockoutCasp1 protein, mouseCaspase 1GasderminsGsdmd protein, mouseInflammasomesInterleukin-18Interleukin-1betaIntracellular Signaling Peptides and ProteinsNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mousePhosphate-Binding ProteinsTlr2 protein, mouseToll-Like Receptor 2

Identifiers

PMID42386736
PMCPMC13462806

What OpenQuestion holds

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Registered trials

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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.