Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Dec;146(14):1796-1802.
doi: 10.1017/S0031182019001069. Epub 2019 Aug 29.

Promastigote secretory gel from natural and unnatural sand fly vectors exacerbate Leishmania major and Leishmania tropica cutaneous leishmaniasis in mice

E Giraud  1 , M Svobodová  2 , I Müller  3 , P Volf  2 , M E Rogers  4
Affiliations

Promastigote secretory gel from natural and unnatural sand fly vectors exacerbate Leishmania major and Leishmania tropica cutaneous leishmaniasis in mice

E Giraud et al. Parasitology. 2019 Dec.

Abstract

Leishmania rely heavily on glycans to complete their digenetic life cycle in both mammalian and phlebotomine sand fly hosts. Leishmania promastigotes secrete a proteophosphoglycan-rich gel (Promastigote Secretory Gel, PSG) that is regurgitated during transmission and can exacerbate infection in the skin. Here we explored the role of PSG from natural Leishmania-sand fly vector combinations by obtaining PSG from Leishmania (L.) major-infected Phlebotomus (P.) papatasi and P. duboscqi and L. tropica-infected P. arabicus. We found that, in addition to the vector's saliva, the PSG from L. major and L. tropica potently exacerbated cutaneous infection in BALB/c mice, improved the probability of developing a patent cutaneous lesion, parasite growth and the evolution of the lesion. Of note, the presence of PSG in the inoculum more than halved the prepatent period of cutaneous L. tropica infection from an average of 32 weeks to 13 weeks. In addition, L. major and L. tropica PSG extracted from the permissive experimental vector, Lutzomyia (Lu.) longipalpis, also exacerbated infections in mice. These results reinforce and extend the hypothesis that PSG is an important and evolutionarily conserved component of Leishmania infection that can be used to facilitate experimental infection for drug and vaccine screening.

Keywords: Cutaneous leishmaniasis; Leishmania; Leishmania major; Leishmania mexicana; Leishmania tropica; PSG; sand fly; transmission; zoonoses.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
The composition of Leishmania glycans within PSG from the permissive vector Lu. longipalpis. Western Blot analysis of L. major, L. tropica and L. mexicana PSG probed with LT15, a mAb which recognizes the Gal-P-Man disaccharide backbone of all Leishmania phosphoglycans (Ilg et al., 1996). Each lane represents the equivalent of one sand fly's PSG extracted from mature infections (L. major and L. tropica, day 12–13 p.i.; L. mexicana day 8 p.i.). The last lane represents the luminal content of one uninfected sand fly midgut probed with LT15. Arrow indicates a junction between stacking and resolving gel. MWM, molecular weight markers.
Fig. 2.
Fig. 2.
L. major infection in mice is exacerbated by the presence of PSG and saliva from natural vectors. L. major PSG was obtained from infected P. papatasi and P. duboscqi sand flies and saliva collected from uninfected flies (P. papatasi: A, C and E; P. duboscqi: B, D and F). One thousand L. major metacyclic promastigotes were injected i.d. into the footpads of BALB/c mice without (open circles) or with 1 µg sterile PSG (closed squares) or 1 µg sterile saliva (open triangles). (A and B) Proportion of mice presenting with cutaneous lesions over the course of study. (C and D) Footpad lesion evolution showing average lesion thickness + s.e.m. (E and F) Final parasite burdens of lesions from footpad homogenates. Each point represents individual mice and bars represent the average value per group. Infections performed in triplicate and representative data is shown, n = 4–5 mice per group. *: P < 0.05; **: P < 0.005 by Mann Whitney unpaired two-tailed t-test.
Fig. 3.
Fig. 3.
L. tropica infection in mice is exacerbated by PSG and saliva from a natural vector. L. tropica PSG was obtained from infected P. arabicus sand flies and saliva collected from uninfected flies. One million L. tropica metacyclic promastigotes were injected i.d. into the rumps of BALB/c mice without (open circles) or with 1 µg sterile PSG (closed squares) or 1 µg sterile saliva (open triangles). (A) Proportion of mice presenting with cutaneous lesions over the course of study. (B) Rump lesion evolution showing total lesion size. (C) Final parasite burdens of lesions from homogenates. Each point represents individual mice. Infections performed in duplicate and representative data is shown, n = 6 mice per group. *: P < 0.05 by Mann Whitney unpaired two-tailed t-test.
Fig. 4.
Fig. 4.
L. major and L. tropica infections in mice are exacerbated by PSG and saliva from the experimental vector, Lu. Longipalpis (L. major: A, C and E; L. tropica: B, D and F). L. tropica and L. major PSG was obtained from infected Lu. longipalpis sand flies and saliva collected from uninfected flies. One thousand L. major metacyclic promastigotes or one million L. tropica metacyclic promastigotes were injected i.d. into the footpads or rumps of BALB/c mice without (open circles) or with 1 µg sterile PSG (closed squares) or with 1 µg sterile saliva (open triangles). (A and B) Proportion of mice presenting with cutaneous lesions over the course of study. (C and D) Lesion evolution showing average lesion thickness + s.e.m or total lesion size. (E and F) Final parasite burdens of lesions from tissue homogenates. Each point represents individual mice and bars represent the average value per group. Representative data is shown of duplicate experiments, n = 6 mice per group. *: P < 0.05; **: P < 0.005 by Mann Whitney unpaired two-tailed t-test.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Anderson CF, Lira R, Kamhawi S, Belkaid Y, Wynn TA and Sacks D (2008) IL-10 and TGF-beta control the establishment of persistent and transmissible infections produced by Leishmania tropica in C57BL/6 mice. Journal of Immunology 180, 4090–4097. - PubMed
    1. Atayde VD, Aslan H, Townsend S, Hassani K, Kamhawi S and Olivier M (2015) Exosome secretion by the parasitic protozoan Leishmania within the sand fly midgut. Cell Reports 13, 957–967. - PMC - PubMed
    1. Badirzadeh A, Taheri T, Taslimi Y, Abdossamadi Z, Heidari-Kharaji M, Gholami E, Sedaghat B, Niyyat M and Rafati S (2017) Arginase activity in pathogenic and non-pathogenic species of Leishmania parasites. PLoS Neglected Tropical Diseases 11, e0005774. - PMC - PubMed
    1. Bates PA (1997) Transmission of Leishmania metacyclic promastigotes by phlebotomine sand flies. International Journal of Parasitology 37, 1097–1106. - PMC - PubMed
    1. Belkaid Y, Kamhawi S, Modi G, Valenzuela J, Noben-Trauth N, Rowton E, Ribeiro J and Sacks DL (1998) Development of a natural model of cutaneous leishmaniasis: powerful effects of vector saliva and saliva pre-exposure on the long-term outcome of Leishmania major infection in the mouse ear dermis. Journal of Experimental Medicine 188, 1941–1953. - PMC - PubMed

Publication types

MeSH terms