Invasion of human microvascular endothelial cells by Mycobacterium leprae through Mce1A protein

Abstract

In patients with lepromatous leprosy, Mycobacterium leprae is often observed inside the human microvascular endothelial cells (HMVEC) surrounding Schwann cells (SC) at the site of lesions in the peripheral nerves. Based on this observation, it is considered that the nasal mucous may be the invasion pathway for M. leprae and HMVEC serve as an important reservoir for the bacteria before they invade SC. In light of previous research which revealed that Mce1A protein mediates bacterial invasion into nasal epithelial cells and HMVEC, we conducted a study to determine whether the invasion of M. leprae into HMVEC can be suppressed by blocking the Mce1A protein. In this study, we analyzed bacterial invasive activity by adding recombinant Escherichia coli, which express the active region (InvX:72 a.a.) of Mce1A protein on their external membrane, into cultured HMVEC, using the adhesin involved in the diffuse adherence mechanism. The number of bacteria that invaded into the cells was then measured by a colony counting method. The active region of Mce1A was divided into four sections, and hyperimmune antisera was prepared for each section for analyzing the inhibitory effect against invasion. The invasive activity was suppressed by antibodies against InvX regions 1–24 a.a., 25–46 a.a. and 58–72 a.a. This suggests that the InvX regions 1–24 a.a., 25–46 a.a. and 58–72 a.a. of Mce1A protein play an important role in the invasion of M. leprae into HMVEC and that it may be possible to suppress entry of M. leprae in HMVEC with antibodies against these regions.

In search of biomarkers for leprosy by unraveling the host immune response to Mycobacterium leprae

“…These four cell types are most likely the first line of defense against M leprae, and tropism for these cells is potentially mediated via mammalian cell entry protein 1A (Mce1A). [50][51][52] Mce1A-specific antibodies have been detected in leprosy patients, especially IgG antibodies were significantly higher in both MB and PB patients compared to controls. 53 This is in contrast to the general assumption that antibodies are predominant in the MB side of the leprosy spectrum only, and Mce1A-specific antibodies therefore show potential for the identification of PB patients as well.…”

“…A proposed route of M leprae entry is via nasal epithelial cells or poorly differentiated keratinocytes, fibroblasts, and endothelial cells of the skin through minor injuries. These four cell types are most likely the first line of defense against M leprae, and tropism for these cells is potentially mediated via mammalian cell entry protein 1A (Mce1A) 50‐52 . Mce1A‐specific antibodies have been detected in leprosy patients, especially IgG antibodies were significantly higher in both MB and PB patients compared to controls 53 .…”