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. 2018 Feb 2;9:134. doi: 10.3389/fimmu.2018.00134

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Copyright © 2018 Silva and Belisle.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Prostaglandin E₂ is hypothesized to exhibit different functions in pauci- and multi-bacillary leprosy patients. Tuberculoid (TT)/borderline tuberculoid (BT) leprosy patients (top panel) display a lower concentration of PGE₂ in comparison with borderline lepromatous (BL)/lepromatous leprosy (LL) patients (lower panel). The lower concentration of PGE₂ in TT/BT patients is hypothesized to facilitate the differentiation of T-helper type 17 (Th17) cells through upregulation of interleukin (IL)-23 cytokine production by dendritic cells. Findings from Yao et al. (44) provide evidence that small amounts of PGE₂ may favor the differentiation of T-helper type 1 (Th1) cells in TT/BT individuals. The levels of PGE₂ in TT/BT patients may also promote the production of nitric oxide (NO) in M. leprae-infected macrophages leading to the control of the bacterial load. In BL/LL patients M. leprae-infected foamy macrophages/Schwann cells produce a higher level of PGE₂ that is hypothesized to inhibit the differentiation of Th1 cells through impairment of the production of IL-12p70 by dendritic cells. The higher concentration of PGD₂, possibly secreted by foamy macrophages/Schwann cells from BL/LL patients, may also inhibit the production of IL-12p70. Additionally, the increased levels of PGE₂ could potentially inhibit the production of IL-23 in dendritic cells, thus blocking the differentiation of Th17 cells. Increased release of insulin-like growth factor I (IGF-I) stimulated via PGE₂ might potentially inhibit NO synthesis and apoptosis. The capacity of PGE₂ to prevent NO production and apoptosis favors the multiplication of M. leprae. The red color represents an intensification or increase in a process or abundance of a product, while the blue color symbolizes an attenuation of the process or product abundance. Arrows with solid lines indicate processes (production/secretion of cytokines, helper T-cell differentiation, apoptosis, and/or mycobacteria survival) that are favored or induced, while an arrow with a hashed line indicates processes that are not favored. (⊢) Represents inhibition of a process or activity.