Trypanosome Infection Establishment in the Tsetse Fly Gut Is Influenced by Microbiome-Regulated Host Immune Barriers
Figure 5
Age and symbiont status modulate trypanosome infection outcomes in the tsetse fly.
Approximately 50% of teneral WT tsetse flies become infected when challenged with trypanosomes. Flies at this stage of development exhibit an immature PM, and present a weak and innocuous innate immune response following parasite challenge. Some teneral tsetse flies are refractory to parasite infections, likely because they acquire more maternally-transmitted PGRP-LB than their susceptible counterparts. Mature GmmWT flies present a vigorous immune response following challenge with trypanosomes and are thus highly resistant to parasite infection. In contrast, age-matched GmmApo flies, which undergo their entire lifecycle (including intrauterine larval development) in the absence of endogenous microbes, are relatively susceptible to trypanosome infection. Although mature GmmApo flies also up-regulate the expression of several immunity-related genes following trypanosome challenge, notably absent from this list is trypanolytic pgrp-lb. Interestingly, the timing of this response also occurs earlier in the infection process in GmmApo compared to GmmWT individuals. We propose that this premature immune response results from the fact that aposymbiotic tsetse house a structurally compromised PM that allows these flies to detect parasites immediately upon entry into the fly's midgut. Our model suggests that symbiotic microbes present in larval tsetse modulate the ability of subsequent adults to produce an intact PM. In turn, this structure regulates trypanosome infection outcomes by controlling the timing of tsetse's immune response following parasite challenge. Other invertebrates, including D. melanogaster and Hirudo verbana (the medicinal leech), house phagocytic cells in their alimentary canal that engulf pathogenic organisms [55], [56]. We speculate that WT tsetse may house similar cells in it's digestive tract that assist in the fly's immune response against trypanosome challenge. PV, proventriculus; BT, bacteriome; GL, gut lumen; EPS, ectoperitrophic space; CP, crop; PM; peritrophic matrix; AMP, antimicrobial peptide; ROS, reactive oxygen species; PGRP-LB, peptidoglycan recognition protein LB.