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. 2009 Jul 21;106(29):12133-8.
doi: 10.1073/pnas.0901226106. Epub 2009 Jul 8.

Interactions between mutualist Wigglesworthia and tsetse peptidoglycan recognition protein (PGRP-LB) influence trypanosome transmission

Jingwen Wang  1 , Yineng Wu, Guangxiao Yang, Serap Aksoy
Affiliations

Interactions between mutualist Wigglesworthia and tsetse peptidoglycan recognition protein (PGRP-LB) influence trypanosome transmission

Jingwen Wang et al. Proc Natl Acad Sci U S A. .

Abstract

Tsetse flies, the sole vectors of African trypanosomes, have coevolved with mutualistic endosymbiont Wigglesworthia glossinidiae. Elimination of Wigglesworthia renders tsetse sterile and increases their trypanosome infection susceptibility. We show that a tsetse peptidoglycan recognition protein (PGRP-LB) is crucial for symbiotic tolerance and trypanosome infection processes. Tsetse pgrp-lb is expressed in the Wigglesworthia-harboring organ (bacteriome) in the midgut, and its level of expression correlates with symbiont numbers. Adult tsetse cured of Wigglesworthia infections have significantly lower pgrp-lb levels than corresponding normal adults. RNA interference (RNAi)-mediated depletion of pgrp-lb results in the activation of the immune deficiency (IMD) signaling pathway and leads to the synthesis of antimicrobial peptides (AMPs), which decrease Wigglesworthia density. Depletion of pgrp-lb also increases the host's susceptibility to trypanosome infections. Finally, parasitized adults have significantly lower pgrp-lb levels than flies, which have successfully eliminated trypanosome infections. When both PGRP-LB and IMD immunity pathway functions are blocked, flies become unusually susceptible to parasitism. Based on the presence of conserved amidase domains, tsetse PGRP-LB may scavenge the peptidoglycan (PGN) released by Wigglesworthia and prevent the activation of symbiont-damaging host immune responses. In addition, tsetse PGRP-LB may have an anti-protozoal activity that confers parasite resistance. The symbiotic adaptations and the limited exposure of tsetse to foreign microbes may have led to the considerable differences in pgrp-lb expression and regulation noted in tsetse from that of closely related Drosophila. A dynamic interplay between Wigglesworthia and host immunity apparently is influential in tsetse's ability to transmit trypanosomes.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Fig. 1.
Fig. 1.
Spatial and temporal expression of pgrp-lb. Adult tissue specific expression in (A) 4 d and (B) 14 d old flies. B: bacteriome; MG: midgut; FB: fat body in male; FB+MKG: fat body and milk duct tubules in female; (C) bacteriome pgrp-lb levels as a function of female age. pgrp-lb levels normalized to host tubulin and presented as fold change relative to the level observed on day 1 prior to blood feeding. (D) Linear regression analysis showing the correlation between Wigglesworthia numbers and pgrp-lb levels from a natural population of G. f. fuscipes (P = 0.019); (E) pgrp-lb levels from dissected bacteriomes of 24 h old and 14 d old GmmWT and GmmWig− adults. Error bars indicate standard error of the mean (SEM) (n = 5).
Fig. 2.
Fig. 2.
Impact of PGRP-LB and PGRP-LC on endosymbiont density and attacin expression. Endosymbiont densities (Sodalis (A) and Wiggleworthia (B)) and attacin levels (C) were measured from normal (N) and dsRNA treated flies: dsPGRP-LC (dsLC), dsPGRP-LB (dsLB) and dsPGRP-LC/LB (dsLB/LC). The relative symbiont densities were normalized according to host tubulin copy number. The levels of attacin were normalized against host tubulin levels and evaluated 20 days after dsRNA treatments. Error bars indicate standard error (n = 4).
Fig. 3.
Fig. 3.
Role of pgrp-lb in host immune activation. (A) Quantification of Northern data showing attacin (attA) abundance in normal and normal E. coli challenged flies by microinjection and in flies that received dsGFP, dsLC and dsLB prior to bacterial challenge. (B) pgrp-lb and (C) pgrp-lc levels in samples analyzed in A, respectively. Error bars indicate standard error (n = 5). Statistically significant results are shown by (*). attacin, pgrp-lb and pgrp-lc levels normalized to β-tubulin. (D) attA abundance in normal and trypanosome challenged flies and in flies treated with dsLC and dsLB prior to per os parasite challenge.
Fig. 4.
Fig. 4.
Regulation of bacteriome pgrp-lb and fat body attacin expression. (A) bacteriome pgrp-lb and (B) fat body attA levels measured from normal and dsRel treated flies with and without E. coli challenge. Error bars indicate standard error (n = 6). Statistically significant results are shown by (*). pgrp-lb and attA expression levels normalized to host β-tubulin.
Fig. 5.
Fig. 5.
pgrp-lb levels and parasite infection prevalence. (A) pgrp-lb levels from dissected bacteriomes of normal (N), trypanosome infected (IF) and trypanosome resistant (RE) flies. Error bars indicate standard error (n = 5). (B) % parasite infection prevalence in flies treated with dsLC and dsLB, respectively. (C) % parasite infection prevalence in dsLC/LB treated flies. P values indicate the level of significance between treatments.
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