Mycobacterial seeding of eye from extrapulmonary organs in a zebrafish model of ocular TB
Purpose
Clinical or radiological evidence of active systemic tuberculosis (TB) is rarely found in patients with tubercular uveitis. We applied a zebrafish (Zf) model of ocular TB to explore a possible role of extrapulmonary niches of mycobacterial infection in seeding of the eye. Dissemination of infection in the Zf model, across anatomical barriers, typically requires infected macrophages (Trojan horse mechanism).
Methods
Zf embryos, 4-days post fertilization (dpf), with intact blood-retinal barriers, were infected with 25 CFUs of Mycobacterium marinum (Mm), through caudal vein microinjections. To compare the role of circulating versus tissue macrophages in seeding mycobacterial infection into the eye, liposomal clodronate (or control liposomes) were injected into caudal veins at 3-dpf to deplete circulating macrophages, and leave Mm infected macrophages only in tissues.
Results
We found a 60% (18 of 30 embryos) ocular infection rate following caudal vein injection of Mm, in transgenic Zf (mpeg:DsRed2) that express red fluorescent protein in macrophages. Five of 18 (27.8%) infections progressed to granuloma formation in the eye. On depleting circulating macrophages with liposomal clodronate injection, we found a 62.5% (25/40) ocular infection rate, though only two (8%) infections progressed to granuloma. In comparison, 39.4% (28/71) infection was noted in fish infected with control liposomes, but four (14.3%) infections progressed to granuloma formation.
Conclusion
Based on these observations, we concluded that Mm-infected tissue macrophages from different organs enter the circulation and seed the eye.
Conflict of interest
No
Author 1
Last name
BASU
Initials of first name(s)
S
City
Bhubaneswar
Country
India
Author 2
Last name
Damera
Initials of first name(s)
SK
City
Bhubaneswar
Country
India
Author 3
Last name
Mitra
Initials of first name(s)
S
City
Bhubaneswar
Country
India
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