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Record W1999072281 · doi:10.1073/pnas.1222264110

Involvement of Toso in activation of monocytes, macrophages, and granulocytes

2013· article· en· W1999072281 on OpenAlexafffund
Karl S. Lang, Philipp A. Lang, Andreas Meryk, Aleksandra A. Pandyra, Louis-Martin Boucher, Vitaly I. Pozdeev, Michael W. Tusche, Joachim R. Göthert, Jillian Haight, Andrew Wakeham, Annick You-Ten, David R. McIlwain, Katja Merches, Vishal Khairnar, Mike Recher, Garry P. Nolan, Yasumichi Hitoshi, Pauline Funkner, Alexander A. Navarini, Admar Verschoor, Namir Shaabani, Nadine Honke, Linda Z. Penn, Pamela S. Ohashi, Dieter Häussinger, Kyeong‐Hee Lee, Tak W. Mak

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2013
Typearticle
Languageen
FieldImmunology and Microbiology
TopicNeutrophil, Myeloperoxidase and Oxidative Mechanisms
Canadian institutionsUniversity Health NetworkOntario Institute for Cancer Research
FundersNational Institute of Allergy and Infectious DiseasesCanadian Institutes of Health ResearchSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung
KeywordsInnate immune systemImmune systemImmunologyLipopolysaccharideSeptic shockCytokineChemistryMicrobiologyPhagocytosisBiologySepsis

Abstract

fetched live from OpenAlex

Rapid activation of immune responses is necessary for antibacterial defense, but excessive immune activation can result in life-threatening septic shock. Understanding how these processes are balanced may provide novel therapeutic potential in treating inflammatory disease. Fc receptors are crucial for innate immune activation. However, the role of the putative Fc receptor for IgM, known as Toso/Faim3, has to this point been unclear. In this study, we generated Toso-deficient mice and used them to uncover a critical regulatory function of Toso in innate immune activation. Development of innate immune cells was intact in the absence of Toso, but Toso-deficient neutrophils exhibited more reactive oxygen species production and reduced phagocytosis of pathogens compared with controls. Cytokine production was also decreased in Toso(-/-) mice compared with WT animals, rendering them resistant to septic shock induced by lipopolysaccharide. However, Toso(-/-) mice also displayed limited cytokine production after infection with the bacterium Listeria monocytogenes that was correlated with elevated presence of Listeria throughout the body. Accordingly, Toso(-/-) mice succumbed to infections of L. monocytogenes, whereas WT mice successfully eliminated the infection. Taken together, our data reveal Toso to be a unique regulator of innate immune responses during bacterial infection and septic shock.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.003

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.033
GPT teacher head0.267
Teacher spread0.234 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations79
Published2013
Admission routes2
Has abstractyes

Explore more

Same venueProceedings of the National Academy of SciencesSame topicNeutrophil, Myeloperoxidase and Oxidative MechanismsFrench-language works237,207