Pseudomonas aeruginosa Stimulates Inflammation and Enhances Kaposi’s Sarcoma Herpesvirus-Induced Cell Proliferation and Cellular Transformation through both Lipopolysaccharide and Flagellin

Author:

Markazi Ashley12,Bracci Paige M.3,McGrath Michael4,Gao Shou-Jiang12

Affiliation:

1. Cancer Virology Program, UPMC Hillman Cancer Center, Pittsburgh, Pennsylvania, USA

2. Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA

3. Department of Epidemiology and Biostatistics, University of California at San Francisco, San Francisco, California, USA

4. The AIDS and Cancer Specimen Resource and Department of Laboratory Medicine, Pathology, and Medicine, University of California at San Francisco, San Francisco, California, USA

Abstract

Kaposi’s sarcoma (KS), caused by infection with 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 , an opportunistic bacterium that can affect AIDS patients, in inflammation and cell proliferation of KSHV-transformed cells. P. aeruginosa 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 P. aeruginosa infection, our work highlights the preventive and therapeutic potential of targeting P. aeruginosa infection in these patients.

Funder

HHS | NIH | National Cancer Institute

HHS | NIH | National Institute of Dental and Craniofacial Research

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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