Related Experiment Video
Updated: May 6, 2026
Phagosome Migration and Velocity Measured in Live Primary Human Macrophages Infected with HIV-1
Published on: September 5, 2016
Flagellin Restricts HIV-1 Infection of Macrophages through Modulation of Viral Entry Receptors and CC Chemokines
Lina Zhou1, Xu Wang1, Qianhao Xiao1
1Department of Pathology and Laboratory Medicine, Temple University Lewis Katz School of Medicine, Philadelphia, PA 19140, USA.
Abstract:
Both bacteria product flagellin and macrophages are implicated in HIV-1 infection/disease progression. However, the impact of their interaction on HIV-1 infection and the associated mechanisms remain to be determined. We thus examined the effect of the flagellins on HIV-1 infection of primary human macrophages. We observed that the pretreatment of macrophages with the flagellins from the different bacteria significantly inhibited HIV-1 infection. The mechanistic investigation showed that the flagellin treatment of macrophages downregulated the major HIV-1 entry receptors (CD4 and CCR5) and upregulated the CC chemokines (MIP-1α, MIP-1β and RANTES), the ligands of CCR5. These effects of the flagellin could be compromised by a toll-like receptor 5 (TLR5) antagonist. Given the important role of flagellin as a vaccine adjuvant in TLR5 activation-mediated immune regulation and in HIV-1 infection of macrophages, future investigations are necessary to determine the in vivo impact of flagellin-TLR5 interaction on macrophage-mediated innate immunity against HIV-1 infection and the effectiveness of flagellin adjuvant-based vaccines studies.
Insights
Flagellins from bacteria inhibit HIV-1 infection in human macrophages by reducing viral entry receptors and increasing protective chemokines. This interaction involves toll-like receptor 5 (TLR5), suggesting potential for flagellin-based vaccine adjuvants.
Area of Science:
- Immunology
- Virology
- Microbiology
Background:
- Flagellin, a bacterial protein, and macrophages play roles in HIV-1 infection.
- The specific impact of flagellin-macrophage interaction on HIV-1 pathogenesis is not fully understood.
Purpose of the Study:
- To investigate the effect of flagellins on HIV-1 infection in primary human macrophages.
- To elucidate the underlying mechanisms of flagellin-mediated modulation of HIV-1 infection.
Main Methods:
- Macrophages were pretreated with flagellins from different bacteria.
- HIV-1 infection levels were assessed.
- Expression of HIV-1 entry receptors (CD4, CCR5) and CC chemokines (MIP-1α, MIP-1β, RANTES) was analyzed.
- The role of toll-like receptor 5 (TLR5) was examined using an antagonist.
Main Results:
- Flagellin pretreatment significantly inhibited HIV-1 infection in macrophages.
- Flagellin treatment downregulated CD4 and CCR5 expression.
- Flagellin treatment upregulated CC chemokines MIP-1α, MIP-1β, and RANTES.
- The observed effects were dependent on TLR5 activation, as shown by antagonism.
Conclusions:
- Flagellins inhibit HIV-1 infection of macrophages through TLR5-mediated downregulation of entry receptors and upregulation of antiviral chemokines.
- Flagellin-TLR5 interactions represent a potential target for enhancing innate immunity against HIV-1.
- Further research is needed to explore flagellin adjuvant-based vaccine strategies for HIV-1 prevention.
