<i>Pseudomonas aeruginosa</i> Stimulates Inflammation and Enhances KSHV-Induced Cell Proliferation and Cellular Transformation through Both LPS and Flagellin
Bibliographic record
Abstract
Abstract Inflammation triggered by innate immunity promotes carcinogenesis in cancer. Kaposi’s sarcoma (KS), a hyperproliferative and inflammatory tumor caused by Kaposi’s sarcoma-associated herpesvirus (KSHV) infection, is the most common cancer in AIDS patients. KSHV infection sensitizes cells to pathogen-associated molecular patterns (PAMPs). We examined the role of Pseudomonas aeruginosa (PA), an opportunistic bacterium that can affect AIDS patients, in inflammation and cell proliferation of KSHV-transformed cells. PA stimulation increased cell proliferation and efficiency of colony formation in softagar of KSHV-transformed rat primary mesenchymal precursor (KMM) cells but had no significant effect on the untransformed (MM) cells. PA stimulation also increased cell proliferation of KSHV-infected human B-cells, Bjab, but not the uninfected cells. Mechanistically, PA stimulation resulted in increased inflammatory cytokines and activation of p38, ERK1/2, and JNK mitogen-activated protein kinase (MAPK) pathways in KMM cells while having no obvious effect on MM cells. PA induction of inflammation and MAPKs were observed with and without inhibition of Toll-like receptor 4 (TLR4) pathway while a flagellin-deleted mutant of PA required a functional TLR4 pathway to induce inflammation and MAPKs. Furthermore, treatment with both LPS or flagellin alone was sufficient to induce inflammatory cytokines, activate MAPKs, and increase cell proliferation and efficiency of colony formation in softagar of KMM cells. These results demonstrate that both LPS and flagellin are PAMPs that contribute to PA induction of inflammation in KSHV-transformed cells. Because AIDS-KS patients are susceptible to PA infection, our work highlights the preventive and therapeutic potential of targeting PA infection in these patients. Importance Kaposi’s sarcoma (KS), caused by infection of Kaposi’s sarcoma-associated herpesvirus (KSHV), is one of the most common cancers in AIDS patients. KS is a highly inflammatory tumor but how KSHV infection induces inflammation remains unclear. We have previously shown that KSHV infection upregulates Toll-like receptor 4 (TLR4), sensitizing cells to lipopolysaccharide (LPS) and Escherichia coli . In the current study, we examined the role of Pseudomonas aeruginosa (PA), an opportunistic bacterium that can affect AIDS patients, in inflammation and cell proliferation of KSHV-transformed cells. PA stimulation increased cell proliferation, inflammatory cytokines, and activation of growth and survival pathways in KSHV-transformed cells through two pathogen-associated molecular patterns LPS and flagellin. Because AIDS-KS patients are susceptible to PA infection, our work highlights the preventive and therapeutic potential of targeting PA infection in these patients.
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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 | 0.001 |
| 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".