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JAMA Ophthalmol. 2014 Jun;132(6):724-9. doi: 10.1001/jamaophthalmol.2014.270.

Replication of Mycobacterium tuberculosis in retinal pigment epithelium.

Author information

1
University of Southern California Eye Institute, Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles.
2
Department of Medicine, The Johns Hopkins University, Baltimore, Maryland3Department of International Health, The Johns Hopkins University, Baltimore, Maryland.

Abstract

IMPORTANCE:

Mycobacterium tuberculosis is an important cause of posterior uveitis in tuberculosis-endemic regions. Clinical and histopathologic evidence suggests that retinal pigment epithelium (RPE) can harbor M tuberculosis. However, the mechanism of M tuberculosis phagocytosis and its growth in RPE is not clear.

OBJECTIVE:

To investigate M tuberculosis phagocytosis, replication, and cytopathic effects in RPE cells compared with macrophages.

DESIGN, SETTING, AND PARTICIPANTS:

Human fetal RPE and monocytic leukemia macrophage (THP-1) cell lines were cultured, and RPE and THP-1 cells were exposed to avirulent M tuberculosis H37Ra. Mycobacteria were added to RPE and THP-1 cells with a 5:1 multiplicity of infection. Nonphagocytized M tuberculosis was removed after 12 hours of exposure (day 0). Cells were harvested at days 0, 1, and 5 to count live and dead cells and intracellular mycobacteria. Toll-like receptor 2 (TLR2) and TLR4 expression was determined by immunohistochemistry; intracellular bacillary load, following TLR2 and TLR4 blockade.

MAIN OUTCOMES AND MEASURES:

Number of intracellular M tuberculosis, cell survival, and TLR2 and TLR4 expression in RPE and THP-1 cells following exposure to M tuberculosis.

RESULTS:

At day 0, an equal number of intracellular M tuberculosis was observed per THP-1 and RPE cells (0.45 and 0.35 M tuberculosis per RPE and THP-1 cells, respectively). Mean (SD) number of intracellular M tuberculosis at day 5 was 1.9 (0.03) and 3.3 (0.01) per RPE and THP-1 cells, respectively (Pā€‰<ā€‰.001). Viability of infected RPE was significantly greater than that of THP-1 cells at day 5 (viable cells: 17 [8%] THP-1 vs 73% [4%] RPE; Pā€‰<ā€‰.05). Expression of TLR2 and TLR4 was detected in both cell types after 12 hours of exposure. Inhibition of TLR2 and TLR4 reduced intracellular M tuberculosis counts in RPE but not in THP-1 cells.

CONCLUSIONS AND RELEVANCE:

Mycobacterium tuberculosis is phagocytized by RPE to a similar extent as in macrophages. However, RPE cells are better able to control bacillary growth and RPE cell survival is greater than that of THP-1 cells following mycobacterial infection, suggesting that RPE can serve as a reservoir for intraocular M tuberculosis infection.

PMID:
24723139
DOI:
10.1001/jamaophthalmol.2014.270
[Indexed for MEDLINE]

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