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HIV-1 infects and alters immune function of a monocyte subset expressing low CD14 surface phenotype
N J Hardegen1, L A Toro, J Muller
1Immunopathology Section, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD, USA.
Abstract:
Monocytes represent a leukocyte subset that express high levels of CD14 on their surface (CD14-high). These cells play a critical role in the pathogenesis of HIV-1 infection. In the present study, we have identified a monocyte subset expressing an extremely low level of CD14 (CD14-low), and examined their susceptibility to HIV-1 infection. Phenotypic analysis by flow cytometry of these cells revealed a low level of CD4, but the absence of CD3, CD14, CD19, and CD83 surface markers. Both CD14-low and CD14-high cell populations expressed CD13 and CD33 markers on their surface, suggesting these cells to be of myeloid origin. Morphologically, CD14-low cells were indistinguishable from CD14-high cells. CD14-low cells were susceptible to infection with a monocytotropic strain of HIV-1 (HIVADA). However, like CD14-high monocytes, CD14-low cells could not be productively infected with a T cell tropic strain of HIV-1 (H9/HTLV(IIIB)). Similar to CD14-high monocytes, CD14-low cells were capable of inducing antigen-stimulated CD4+ T-cell proliferation. HIV-1 infection substantially reduced their ability to induce antigen-stimulated T-cell proliferation. These data indicate that CD14-low cells belong to the monocyte lineage and may play an important role in the immunopathogenesis of HIV-1 infection.
Insights
Researchers discovered a new monocyte subset (CD14-low) susceptible to HIV-1 infection. These cells, similar to CD14-high monocytes, can stimulate T-cell proliferation, which is impaired by HIV-1 infection, highlighting their role in disease pathogenesis.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Monocytes, a leukocyte subset expressing high CD14 (CD14-high), are crucial in HIV-1 pathogenesis.
- A distinct monocyte subset with extremely low CD14 expression (CD14-low) was identified.
Purpose of the Study:
- To investigate the susceptibility of CD14-low monocytes to HIV-1 infection.
- To determine the role of CD14-low monocytes in HIV-1 immunopathogenesis.
Main Methods:
- Flow cytometry for phenotypic analysis of CD14-low and CD14-high monocytes.
- Infection assays with monocytotropic (HIVADA) and T-cell tropic (H9/HTLV(IIIB)) HIV-1 strains.
- Assessment of antigen-stimulated CD4+ T-cell proliferation induced by both monocyte subsets.
Main Results:
- CD14-low monocytes express CD13 and CD33, indicating myeloid origin, and are morphologically similar to CD14-high monocytes.
- CD14-low monocytes are susceptible to HIVADA infection but not H9/HTLV(IIIB).
- HIV-1 infection significantly reduced the capacity of CD14-low monocytes to induce antigen-stimulated T-cell proliferation, similar to CD14-high monocytes.
Conclusions:
- CD14-low cells are part of the monocyte lineage.
- CD14-low monocytes are susceptible to certain HIV-1 strains and play a role in HIV-1 immunopathogenesis by influencing T-cell responses.