Inhibitor of serine peptidase 2 enhances Leishmania major survival in the skin through control of monocytes and monocyte‐derived cells. Issue 3 (3rd January 2018)
- Record Type:
- Journal Article
- Title:
- Inhibitor of serine peptidase 2 enhances Leishmania major survival in the skin through control of monocytes and monocyte‐derived cells. Issue 3 (3rd January 2018)
- Main Title:
- Inhibitor of serine peptidase 2 enhances Leishmania major survival in the skin through control of monocytes and monocyte‐derived cells
- Authors:
- Goundry, Amy
Romano, Audrey
Lima, Ana Paula C. A.
Mottram, Jeremy C.
Myburgh, Elmarie - Abstract:
- 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 2Abstract : 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. FASEB J. 32, 1315‐1327 (2018). www.fasebj.org … (more)
- Is Part Of:
- FASEB journal. Volume 32:Issue 3(2018)
- Journal:
- FASEB journal
- Issue:
- Volume 32:Issue 3(2018)
- Issue Display:
- Volume 32, Issue 3 (2018)
- Year:
- 2018
- Volume:
- 32
- Issue:
- 3
- Issue Sort Value:
- 2018-0032-0003-0000
- Page Start:
- 1315
- Page End:
- 1327
- Publication Date:
- 2018-01-03
- Subjects:
- inflammatory monocytes -- parasite -- dermis -- leishmaniasis -- in vivo
Biology -- Periodicals
Biology, Experimental -- Periodicals
570 - Journal URLs:
- http://onlinelibrary.wiley.com/ ↗
- DOI:
- 10.1096/fj.201700797R ↗
- Languages:
- English
- ISSNs:
- 0892-6638
- Deposit Type:
- Legaldeposit
- View Content:
- Available online (eLD content is only available in our Reading Rooms) ↗
- Physical Locations:
- British Library DSC - BLDSS-3PM
British Library HMNTS - ELD Digital store - Ingest File:
- 13227.xml