<i>Cnes2b</i> Regulates Host Resistance, Inflammatory Responses and Tissue Damage Following <i>Cryptococcus deneoformans</i> Infection
Bibliographic record
Abstract
Abstract The 32.1 Mb Cnes2 chromosome 17 interval was shown to confer resistance to progressive Cryptococcus deneoformans 52D infection. To refine the location of Cnes2 host resistance genes, a subcongenic mouse strain (B6.CBA- Cnes2b ) that contains 8.7 Mb from the telomeric region of Cnes2 was created. At 28 days postinfection B6.CBA- Cnes2b mice had a lower lung fungal burden, increased lung injury, as well as mortality compared to C57BL/6N. B6.CBA- Cnes2b mice had increased pulmonary production of pro-inflammatory mediators, chemokines and Th1-type cytokines as well as increased recruitment of monocytes and neutrophils to the lungs. Cnes2b also regulated several elements of the host response to C. deneoformans 52D infection in a sex-dependent manner. Specifically, male B6.CBA- Cnes2b mice had a lower lung fungal burden, increased brain injury and mortality relative to females. Taken together these findings demonstrate that Cnes2b regulates host inflammation in a manner that controls fungal burden and increases tissue damage. Precise identification of the genes encoded by Cnes2b could reveal key mechanisms of cryptococcal host resistance and immune reconstitution or postinfectious inflammatory syndromes. Importance The 32.1 Mb Cnes2 congenic interval from chromosome 17 of resistant CBA/J mice regulates host resistance to C. deneoformans 52D infection. This study characterizes the host response of B6.CBA- Cnes2b mice that carry an 8.7 Mb sub-congenic interval derived from Cnes2 following C. deneoformans 52D infection. B6.CBA- Cnes2b mice had reduced lung fungal burden, increased lung and brain injury, and mortality. The effects of Cnes2b differed between male and female subcongenic mice and are consistent with known sex differences in human cryptococcal disease. The host response of B6.CBA- Cnes2b mice reflects a crucial balance between effective control of fungal burden and potentially deleterious consequences of enhanced inflammation during cryptococcal infection as predicted by the damage response framework. Further analysis of the Cnes2b sub-congenic interval will lead to definitive identification of genes that confer resistance to progressive cryptococcal infection and/or contribute to deleterious inflammatory responses. Defining key mechanisms that regulate the immune response to Cryptococcus sp. is an important step towards the development of host-directed therapeutics that could improve disease outcomes.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot 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.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
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.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".