Human Mast Cell Progenitors Can Be Infected by Macrophagetropic Human Immunodeficiency Virus Type 1 and Retain Virus with Maturation In Vitro
- 15 November 2001
- journal article
- research article
- Published by American Society for Microbiology in Journal of Virology
- Vol. 75 (22), 10808-10814
- https://doi.org/10.1128/jvi.75.22.10808-10814.2001
Abstract
Mast cells are critical components of innate and adaptive immunity that differentiate in tissues in situ from circulating committed progenitor cells. We now demonstrate that human cord blood-derived mast cell progenitors are susceptible to infection with macrophagetropic (M-tropic) and dualtropic human immunodeficiency virus type 1 (HIV-1) isolates but not with T-cell-tropic (T-tropic) strains. Mast cell progenitors (c-kit+CD13+cells with chloroacetate esterase activity) were purified from 4-week-old cultures of cord blood mononuclear cells maintained in stem cell factor, interleukin-6 (IL-6), and IL-10 using a CD14 depletion column. These progenitors expressed CCR3, CCR5, and CXCR4, as well as low levels of CD4. When infected in vitro with viruses pseudotyped with different HIV and simian immunodeficiency virus envelope glycoproteins, only M-tropic and dualtropic, but not T-tropic, viruses were able to enter mast cell progenitors. Both the CCR5-specific monoclonal antibody 2D7 and TAK-779, a nonpeptide inhibitor of CCR5-mediated viral entry, blocked HIV-1 strain ADA infection by >80%. Cultures infected with replication-competent virus produced progressively increasing amounts of virus for 21 days as indicated by p24 antigen detection. Mast cell progenitors that were exposed to an M-tropic, green fluorescent protein-expressing HIV-1 strain exhibited fluorescence indicative of viral entry and replication on a single-cell level and retained virus production during differentiation. The trafficking of mast cell progenitors to multiple tissues, combined with the long life span of mature mast cells, suggests that they could provide a widespread and persistent HIV reservoir in AIDS.Keywords
This publication has 29 references indexed in Scilit:
- Mast cell activation and migration to lymph nodes during induction of an immune response in mice.JCI Insight, 1998
- CCR3 and CCR5 are co-receptors for HIV-1 infection of microgliaNature, 1997
- Efficient Interaction of HIV-1 with Purified Dendritic Cells via Multiple Chemokine CoreceptorsThe Journal of Experimental Medicine, 1996
- A Dual-Tropic Primary HIV-1 Isolate That Uses Fusin and the β-Chemokine Receptors CKR-5, CKR-3, and CKR-2b as Fusion CofactorsCell, 1996
- The β-Chemokine Receptors CCR3 and CCR5 Facilitate Infection by Primary HIV-1 IsolatesCell, 1996
- Spectrum of Morphologic Changes of Lymph Nodes in HIV InfectionMemórias do Instituto Oswaldo Cruz, 1996
- Mast cell modulation of neutrophil influx and bacterial clearance at sites of infection through TNF-αNature, 1996
- Mast cells in the brain: evidence and functional significanceTrends in Neurosciences, 1996
- Human Immunodeficiency Virus and the Skin: Selected Controversies.Journal of Investigative Dermatology, 1995
- Direct evidence of a role for mast cells in the pathogenesis of antigen-induced bronchoconstriction.JCI Insight, 1987