Goundry, A., Romano, A., Lima, A. P. C.A., Mottram, J. and Myburgh, E. (2018) Inhibitor of serine peptidase 2 enhances Leishmania major survival in the skin through control of monocytes and monocyte-derived cells. FASEB Journal, 32(3), pp. 1315-1327. (doi: 10.1096/fj.201700797R) (PMID:29097502) (PMCID:PMC5892728)
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Abstract
Leishmania major is the causative agent of the neglected tropical disease, cutaneous leishmaniasis. In the mouse, protective immunity to Leishmania is associated with inflammatory responses. Here, we assess the dynamics of the inflammatory responses at the lesion site during experimental long-term, low-dose intradermal infection of the ear, employing noninvasive imaging and genetically modified L. major. Significant infiltrates of neutrophils and monocytes occurred at 1–4 d and 2–4 wk, whereas dermal macrophage and dendritic cell (DC) numbers were only slightly elevated in the first days. Quantitative whole-body bioluminescence imaging of myeloperoxidase activity and the quantification of parasite loads indicated that the Leishmania virulence factor, inhibitor of serine peptidase 2 (ISP2), is required to modulate phagocyte activation and is important for parasite survival at the infection site. ISP2 played a role in the control of monocyte, monocyte-derived macrophage, and monocyte-derived DC (moDC) influx, and was required to reduce iNOS expression in monocytes, monocyte-derived cells, and dermal DCs; the expression of CD80 in moDCs; and levels of IFN-γ in situ. Our findings indicate that the increased survival of L. major in the dermis during acute infection is associated with the down-regulation of inflammatory monocytes and monocyte-derived cells via ISP2.—Goundry, A., Romano, A., Lima, A. P. C. A., Mottram, J. C., Myburgh, E. Inhibitor of serine peptidase 2 enhances Leishmania major survival in the skin through control of monocytes and monocyte-derived cells.
| Item Type: | Articles |
|---|---|
| Status: | Published |
| Refereed: | Yes |
| Glasgow Author(s) Enlighten ID: | Goundry, Miss Amy Louise and Lima, Dr Ana and Myburgh, Dr Elmarie and Mottram, Professor Jeremy |
| Authors: | Goundry, A., Romano, A., Lima, A. P. C.A., Mottram, J., and Myburgh, E. |
| College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity |
| Journal Name: | FASEB Journal |
| Publisher: | Federation of American Society of Experimental Biology |
| ISSN: | 0892-6638 |
| ISSN (Online): | 1530-6860 |
| Published Online: | 02 November 2017 |
| Copyright Holders: | Copyright © 2017 The Authors |
| First Published: | First published in FASEB Journal 32(3):1315-1327 |
| Publisher Policy: | Reproduced under a Creative Commons License |
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