1. Fig. 1. Exposure to P. duboscqi uninfected sand flies (USFs) induces an anti-saliva immunity that protects NHP from vector-transmitted CL.
Exposure to P. duboscqi uninfected sand flies (USFs) induces an anti-saliva immunity that protects NHP from vector-transmitted CL. (A to C) Immunity to USF bites 48 hours (A and B) or 2 weeks (C) after the last exposure. (A) DTH response (left panel) and a hematoxylin and eosin–stained biopsy section (right panel, ×400) from a USF bite site. (B) IFN-γ mRNA expression in biopsies of a USF bite site (Exp. Bites) or normal skin (Naïve) from the same animal. Biopsies were obtained from six randomly selected bite site–reactive NHP (P = , Mann-Whitney test; n = 6). (C) Anti-saliva immunoglobulin G (IgG) levels before (Pre) or after (Post) exposure (P = , t test; n = 10). Cumulative data from two independent experiments are shown. OD, optical density. (D to K) Fifteen USF-exposed NHP (Exp. Bites) and nine naïve NHP were challenged with 50 L. major–infected P. duboscqi. Cumulative data from two independent experiments are shown. (D) Disease burden (P = , Mann-Whitney test; n = 9 to 15). (E) Maximum lesion size (P = , Mann-Whitney test; n = 9 to 15). (F) Kaplan-Meier plot of the healing time, a cumulative measurement of lesion development from ulcer to scar [P = , log-rank (Mantel-Cox) test; n = 9 to 15]. (G) Representative photographs 9 weeks after challenge. (H) Parasite number 12 weeks after challenge (P = , Mann-Whitney test; n = 9 to 15). (I to K) PBMCs from seven naïve (Naïve) and nine USF-exposed NHP (Exp. Bites) were stimulated with Leishmania antigen (Leish) 2 weeks after challenge. Selection was based on cell number and viability. (I) IFN-γ SFC by enzyme-linked immunospot (ELISPOT) (P = , Mann-Whitney test; n = 7 to 9). (J) Percent of CD4+IFN-γ+ lymphocytes by flow cytometry (P = , Mann-Whitney test; n = 7 to 9). (K) Frequency of CD4+IFN-γ+ lymphocytes correlated to disease burden. Dashed line indicates 95% confidence interval (CI) (P = , n = 16, Spearman test r = −0.72). Scale bar, 200 μm; lines and bars indicate the mean, and error bars indicate SEM.
Fabiano Oliveira et al., Sci Transl Med 2015;7:290ra90
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