A21 ANTIBIOTICS SUPPRESS INTESTINAL ANTIVIRAL RESPONSES IN A MICROBIOTA-INDEPENDENT MANNER
Bibliographic record
Abstract
Oral antibiotics are commonly administered to mice, and effects seen following these treatments are typically ascribed to the depletion of the intestinal microbiota; however, these effects may also be due to direct effects of the antibiotics on the host. In vitro studies have shown that various antibiotics can suppress many immune functions, but despite the frequent use of antibiotics in the clinic and research, potential microbiota-independent effects of antibiotics in vivo have been understudied. Here, we use murine norovirus strain CR6 (MNV-CR6) to investigate the effects of an oral antibiotic cocktail on intestinal immune responses. MNV-CR6 forms a persistent infection limited to the murine colon, a site containing high numbers of antibiotic-sensitive microbes which have been suggested to influence antiviral immunity. Importantly, while MNV-CR6 provokes an antiviral CD8+ T cell response, the magnitude of this response has no observed effect on the course of the infection, allowing us to study the effects of antibiotics on antiviral immunity without significantly influencing the underlying infection. We aimed to investigate the effects of an oral antibiotic cocktail on antiviral immune responses to MNV-CR6 infection, including whether antibiotic-mediated effects were microbiota-dependent. Conventional (CNV) and Germ-Free (GF) C57Bl/6J mice were administered a cocktail of ampicillin, gentamicin, metronidazole, neomycin, and vancomycin in drinking water for two weeks prior to oral infection with MNV-CR6. At 11 days post-infection, lymphocytes were isolated from the colon and tetramer stained to identify MNV-specific CD8+ T cells. Viral loads were assessed by qPCR of colon tissue. To determine whether the microbiota is necessary for MNV-CR6 infection, we infected CNV and GF mice with MNV-CR6 and assessed viral loads. GF status did not significantly impact viral load, indicating that the microbiota is dispensable for MNV-CR6 infection. Similarly, we assessed the effect of antibiotics on viral load. In both CNV and GF mice, antibiotic treatment did not significantly impact viral load. Next, we assessed the effects of antibiotics on the generation of an antiviral CD8+ T cell response to MNV-CR6. CNV and GF mice were treated with an oral antibiotic cocktail prior to infection with MNV-CR6, and lymphocytes were isolated from the colon. While untreated mice generated MNV-specific CD8+ T cells, antibiotics prevented this response. Importantly, this effect was seen in both CNV and GF mice, indicating that the effect of the antibiotic treatment was microbiota-independent. Our results indicate that antibiotic treatment can profoundly suppress antiviral immune responses in a microbiota-independent manner. These results may have implications for the use of antibiotics clinically and in microbiota research. CIHR
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 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".