PGRP-LB is a maternally transmitted immune milk protein that influences symbiosis and parasitism in tsetse’s offspring

Abstract

Beneficial microbe functions range from host dietary supplementation to development and maintenance of host immune system. In mammals, newborn progeny are quickly colonized with a symbiotic fauna that is provisioned in mother's milk and that closely resembles that of the parent. Tsetse fly (Diptera: Glossinidae) also depends on the obligate symbiont Wigglesworthia for nutritional supplementation, optimal fecundity, and immune system development. Tsetse progeny develop one at a time in an intrauterine environment and receive nourishment and symbionts in mother's milk. We show that the host Peptidoglycan Recognition Protein (PGRP-LB) is expressed only in adults and is a major component of the milk that nourishes the developing progeny. The amidase activity associated with PGRP-LB may scavenge the symbiotic peptidoglycan and prevent the induction of tsetse's Immune Deficiency pathway that otherwise can damage the symbionts. Reduction of PGRP-LB experimentally diminishes female fecundity and damages Wigglesworthia in the milk through induction of antimicrobial peptides, including Attacin. Larvae that receive less maternal PGRP-LB give rise to adults with fewer Wigglesworthia and hyperimmune responses. Such adults also suffer dysregulated immunity, as indicated by the presence of higher trypanosome densities in parasitized adults. We show that recPGRP-LB has antimicrobial and antitrypanosomal activities that may regulate symbiosis and impact immunity. Thus, PGRP-LB plays a pivotal role in tsetse's fitness by protecting symbiosis against host-inflicted damage during development and by controlling parasite infections in adults that can otherwise reduce host fecundity. maternal transfer | transgenerational immune effects | antimicrobial activity | antitrypanosomal activity

Analysis of Multiple Tsetse Fly Populations in Uganda Reveals Limited Diversity and Species-Specific Gut Microbiota

“…In laboratory studies, Wigglesworthia density has been shown to influence host traits for resistance to trypanosome infections through the induction of a host immune protein, peptidoglycan recognition protein LB (PGRP-LB) (66). The same host factor, PGRP-LB, was also shown to exhibit antibacterial activity in vitro (66,67). Thus, the various Wigglesworthia densities found in natural populations could impact the vector competence of these individuals and species and the ability of other microbes to survive in their guts.…”

Interwoven Biology of the Tsetse Holobiont

“…PGRP-LB is maternally transmitted via milk secretions to developing offspring and is produced by adult flies only after their first blood meal (123). This protein also exhibits trypanocidal activity (123). Therefore, higher levels of PGRP-LB may aid in the refractory nature of older, nonteneral flies with respect to trypanosome infection.…”

“…The host pathogen recognition protein PGRP-LB, which scavenges peptidoglycan, thus preventing immune deficiency (IMD) signaling pathway stimulation, is intimately associated with maintaining the Wigglesworthia symbiosis (56,123). PGRP-LB is maternally transmitted via milk secretions to developing offspring and is produced by adult flies only after their first blood meal (123). This protein also exhibits trypanocidal activity (123).…”

“…For example, the contribution of the tsetse fly's immune system to the persistence of the Wigglesworthia symbiosis may also play a role in the fly's ability to transmit trypanosomes. The host pathogen recognition protein PGRP-LB, which scavenges peptidoglycan, thus preventing immune deficiency (IMD) signaling pathway stimulation, is intimately associated with maintaining the Wigglesworthia symbiosis (56,123). PGRP-LB is maternally transmitted via milk secretions to developing offspring and is produced by adult flies only after their first blood meal (123).…”

The Tsetse Fly Obligate Mutualist Wigglesworthia morsitans Alters Gene Expression and Population Density via Exogenous Nutrient Provisioning

“…Reductions in W. morsitans population density were also observed following vitamin administration, possibly either due to symbiont recognition of a decreased need or, more likely, particularly in light of the drastic genome reduction of W. morsitans, through host modulation. In support of more-probable host-mediated control, components of the tsetse immune system, notably the peptidoglycan recognition protein (PGRP-LB), have been shown to control the abundance of the W. morsitans symbiont (52,53). In further support of host influence, modeling and experimental studies of the Buchnera and aphid symbiosis suggest that alterations in nutritional phenotypes may be directed by variation in the host's capacity to supply precursors to symbionts rather than differences in symbiont genomic capabilities (15,22,51).…”