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Tsetse immune system maturation requires the presence of obligate symbionts in larvae.

Weiss BL, Wang J, Aksoy S - PLoS Biol. (2011)

Bottom Line: Adults that lack Wigglesworthia during larval development exhibit exceptionally compromised cellular and humoral immune responses following microbial challenge, including reduced expression of genes that encode antimicrobial peptides (cecropin and attacin), hemocyte-mediated processes (thioester-containing proteins 2 and 4 and prophenoloxidase), and signal-mediating molecules (inducible nitric oxide synthase).Furthermore, Gmm(Wgm-) adults harbor a reduced population of sessile and circulating hemocytes, a phenomenon that likely results from a significant decrease in larval expression of serpent and lozenge, both of which are associated with the process of early hemocyte differentiation.Our results demonstrate that Wigglesworthia must be present during the development of immature progeny in order for the immune system to function properly in adult tsetse.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology and Public Health, Division of Epidemiology of Microbial Diseases, Yale University School of Medicine, New Haven, Connecticut, United States of America. brian.weiss@yale.edu

ABSTRACT
Beneficial microbial symbionts serve important functions within their hosts, including dietary supplementation and maintenance of immune system homeostasis. Little is known about the mechanisms that enable these bacteria to induce specific host phenotypes during development and into adulthood. Here we used the tsetse fly, Glossina morsitans, and its obligate mutualist, Wigglesworthia glossinidia, to investigate the co-evolutionary adaptations that influence the development of host physiological processes. Wigglesworthia is maternally transmitted to tsetse's intrauterine larvae through milk gland secretions. We can produce flies that lack Wigglesworthia (Gmm(Wgm-) yet retain their other symbiotic microbes. Such offspring give rise to adults that exhibit a largely normal phenotype, with the exception being that they are reproductively sterile. Our results indicate that when reared under normal environmental conditions Gmm(Wgm-) adults are also immuno-compromised and highly susceptible to hemocoelic E. coli infections while age-matched wild-type individuals are refractory. Adults that lack Wigglesworthia during larval development exhibit exceptionally compromised cellular and humoral immune responses following microbial challenge, including reduced expression of genes that encode antimicrobial peptides (cecropin and attacin), hemocyte-mediated processes (thioester-containing proteins 2 and 4 and prophenoloxidase), and signal-mediating molecules (inducible nitric oxide synthase). Furthermore, Gmm(Wgm-) adults harbor a reduced population of sessile and circulating hemocytes, a phenomenon that likely results from a significant decrease in larval expression of serpent and lozenge, both of which are associated with the process of early hemocyte differentiation. Our results demonstrate that Wigglesworthia must be present during the development of immature progeny in order for the immune system to function properly in adult tsetse. This phenomenon provides evidence of yet another important physiological adaptation that further anchors the obligate symbiosis between tsetse and Wigglesworthia.

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The effect of symbiont status on melanization in tsetse.Mature GmmWT andGmmWgm− tsetse(n  = 10 of each strain) wereintra-thoracically inoculated with 1×103E. coli K12. Thirty minutes post-inoculation the wound site onindividuals from each strain was inspected microscopically for the presence ofhemolymph clotting and melanin deposition. Thirty minutes post-inoculation,neither hemolymph clotting nor melanin were observed at the wound site ofGmmWgm− individuals(indicated by a red arrow). In contrast, within the same amount of time,hemolymph no longer exuded from the wound of WT flies and melanin was presentsurrounding the site (indicted by a white arrow).
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pbio-1000619-g004: The effect of symbiont status on melanization in tsetse.Mature GmmWT andGmmWgm− tsetse(n  = 10 of each strain) wereintra-thoracically inoculated with 1×103E. coli K12. Thirty minutes post-inoculation the wound site onindividuals from each strain was inspected microscopically for the presence ofhemolymph clotting and melanin deposition. Thirty minutes post-inoculation,neither hemolymph clotting nor melanin were observed at the wound site ofGmmWgm− individuals(indicated by a red arrow). In contrast, within the same amount of time,hemolymph no longer exuded from the wound of WT flies and melanin was presentsurrounding the site (indicted by a white arrow).

Mentions: A notable result of our immunity-related gene expression analysis was a 37-folddecrease in PPO levels inGmmWgm− flies. This enzyme is anessential component of the melanization pathway, and its expression ultimatelyresults in host wound healing and the melanization, encapsulation, and subsequentremoval of foreign microorganisms [26]–[28]. In conjunction with the remarkable variation inPPO expression observed between GmmWTand GmmWgm−, we were also able tovisually observe the absence of a melanization response to E. coliinfection in flies lacking Wigglesworthia. In fact, 30 minpost-injection with E. coli, hemolymph was still actively exudingfrom the inoculation wound of GmmWgm−flies. Conversely, in WT individuals no hemolymph was detectable and melanin wasdeposited at the wound site (Figure4). These results further suggest that hemocyte-mediated cellular immunityprovides an imperative defense against the establishment of bacterial infections intsetse's hemocoel. Furthermore, the absence of this response inGmmWgm− individuals was likelyresponsible for the compromised host survival phenotype we observed followinginfection with E. coli.


Tsetse immune system maturation requires the presence of obligate symbionts in larvae.

Weiss BL, Wang J, Aksoy S - PLoS Biol. (2011)

The effect of symbiont status on melanization in tsetse.Mature GmmWT andGmmWgm− tsetse(n  = 10 of each strain) wereintra-thoracically inoculated with 1×103E. coli K12. Thirty minutes post-inoculation the wound site onindividuals from each strain was inspected microscopically for the presence ofhemolymph clotting and melanin deposition. Thirty minutes post-inoculation,neither hemolymph clotting nor melanin were observed at the wound site ofGmmWgm− individuals(indicated by a red arrow). In contrast, within the same amount of time,hemolymph no longer exuded from the wound of WT flies and melanin was presentsurrounding the site (indicted by a white arrow).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3104962&req=5

pbio-1000619-g004: The effect of symbiont status on melanization in tsetse.Mature GmmWT andGmmWgm− tsetse(n  = 10 of each strain) wereintra-thoracically inoculated with 1×103E. coli K12. Thirty minutes post-inoculation the wound site onindividuals from each strain was inspected microscopically for the presence ofhemolymph clotting and melanin deposition. Thirty minutes post-inoculation,neither hemolymph clotting nor melanin were observed at the wound site ofGmmWgm− individuals(indicated by a red arrow). In contrast, within the same amount of time,hemolymph no longer exuded from the wound of WT flies and melanin was presentsurrounding the site (indicted by a white arrow).
Mentions: A notable result of our immunity-related gene expression analysis was a 37-folddecrease in PPO levels inGmmWgm− flies. This enzyme is anessential component of the melanization pathway, and its expression ultimatelyresults in host wound healing and the melanization, encapsulation, and subsequentremoval of foreign microorganisms [26]–[28]. In conjunction with the remarkable variation inPPO expression observed between GmmWTand GmmWgm−, we were also able tovisually observe the absence of a melanization response to E. coliinfection in flies lacking Wigglesworthia. In fact, 30 minpost-injection with E. coli, hemolymph was still actively exudingfrom the inoculation wound of GmmWgm−flies. Conversely, in WT individuals no hemolymph was detectable and melanin wasdeposited at the wound site (Figure4). These results further suggest that hemocyte-mediated cellular immunityprovides an imperative defense against the establishment of bacterial infections intsetse's hemocoel. Furthermore, the absence of this response inGmmWgm− individuals was likelyresponsible for the compromised host survival phenotype we observed followinginfection with E. coli.

Bottom Line: Adults that lack Wigglesworthia during larval development exhibit exceptionally compromised cellular and humoral immune responses following microbial challenge, including reduced expression of genes that encode antimicrobial peptides (cecropin and attacin), hemocyte-mediated processes (thioester-containing proteins 2 and 4 and prophenoloxidase), and signal-mediating molecules (inducible nitric oxide synthase).Furthermore, Gmm(Wgm-) adults harbor a reduced population of sessile and circulating hemocytes, a phenomenon that likely results from a significant decrease in larval expression of serpent and lozenge, both of which are associated with the process of early hemocyte differentiation.Our results demonstrate that Wigglesworthia must be present during the development of immature progeny in order for the immune system to function properly in adult tsetse.

View Article: PubMed Central - PubMed

Affiliation: Department of Epidemiology and Public Health, Division of Epidemiology of Microbial Diseases, Yale University School of Medicine, New Haven, Connecticut, United States of America. brian.weiss@yale.edu

ABSTRACT
Beneficial microbial symbionts serve important functions within their hosts, including dietary supplementation and maintenance of immune system homeostasis. Little is known about the mechanisms that enable these bacteria to induce specific host phenotypes during development and into adulthood. Here we used the tsetse fly, Glossina morsitans, and its obligate mutualist, Wigglesworthia glossinidia, to investigate the co-evolutionary adaptations that influence the development of host physiological processes. Wigglesworthia is maternally transmitted to tsetse's intrauterine larvae through milk gland secretions. We can produce flies that lack Wigglesworthia (Gmm(Wgm-) yet retain their other symbiotic microbes. Such offspring give rise to adults that exhibit a largely normal phenotype, with the exception being that they are reproductively sterile. Our results indicate that when reared under normal environmental conditions Gmm(Wgm-) adults are also immuno-compromised and highly susceptible to hemocoelic E. coli infections while age-matched wild-type individuals are refractory. Adults that lack Wigglesworthia during larval development exhibit exceptionally compromised cellular and humoral immune responses following microbial challenge, including reduced expression of genes that encode antimicrobial peptides (cecropin and attacin), hemocyte-mediated processes (thioester-containing proteins 2 and 4 and prophenoloxidase), and signal-mediating molecules (inducible nitric oxide synthase). Furthermore, Gmm(Wgm-) adults harbor a reduced population of sessile and circulating hemocytes, a phenomenon that likely results from a significant decrease in larval expression of serpent and lozenge, both of which are associated with the process of early hemocyte differentiation. Our results demonstrate that Wigglesworthia must be present during the development of immature progeny in order for the immune system to function properly in adult tsetse. This phenomenon provides evidence of yet another important physiological adaptation that further anchors the obligate symbiosis between tsetse and Wigglesworthia.

Show MeSH
Related in: MedlinePlus