The MSHA strain of Pseudomonas aeruginosa activated TLR pathway and enhanced HIV-1 DNA vaccine immunoreactivity.
The mannose-sensitive hemagglutination pilus strain of Pseudomonas aeruginosa (PA-MSHA) has been shown to trigger naïve immune responses through the activation of monocytes, macrophages, natural killer cells (NK cells) and antigen presenting cells (APCs). Based on the hypothesis that PA-MSHA activates natural immunity through the Toll-like receptor (TLR) pathway, we scanned several critical TLR pathway molecules in mouse splenocytes using high-throughput real-time QRT-PCR and co-stimulatory molecule in bone marrow-derived dendritic cells (BMDCs) following in vitro stimulation by PA-MSHA. PA-MSHA enabled activation of the TLR pathway mediated by NF-κB and JNK signaling in splenocytes, and the co-stimulatory molecule CD86 was up-regulated in BMDCs. We then assessed the adjuvant effect of PA-MSHA for HIV-1 DNA vaccines. In comparison to DNA inoculation alone, co-inoculation with low dosage of PA-MSHA enhanced specific immunoreactivity against HIV-1 Env in both cellular and humoral responses, and promoted antibody avidity maturation. However, high doses of adjuvant resulted in an immunosuppressive effect; a two- or three-inoculation regimen yielded low antibody responses and the two-inoculation regimen exhibited only a slight cellular immunity response. To our knowledge, this is the first report demonstrating the utility of PA-MSHA as an adjuvant to a DNA vaccine. Further research is needed to investigate the exact mechanisms through which PA-MSHA achieves its adjuvant effects on innate immune responses, especially on dendritic cells.
State Key Laboratory for Infectious Disease Prevention and Control, National Center for AIDS/STD Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, China.
Jue
J
Hou
Yong
Y
Liu
Ying
Y
Liu
Yiming
Y
Shao
D000276:Adjuvants, Immunologic; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D007113:Immunity, Innate; D007694:Killer Cells, Natural / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D051379:Mice; D009000:Monocytes / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D011550:Pseudomonas aeruginosa / Q000276:immunology / Q000472:pathogenicity; D015398:Signal Transduction; D051193:Toll-Like Receptors / Q000378:metabolism; D019444:Vaccines, DNA / Q000235:genetics / Q000276:immunology; D054299:env Gene Products, Human Immunodeficiency Virus / Q000276:immunology
D000276:Adjuvants, Immunologic; D016328:NF-kappa B; D051193:Toll-Like Receptors; D019444:Vaccines, DNA; D054299:env Gene Products, Human Immunodeficiency Virus