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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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Wigglesworthia modulates the development and function oftsetse's immune system.Through a currently unknown mechanism, the presence ofWigglesworthia in GmmWT larvaestimulates hemocyte differentiation in a specialized organ that is homologous toDrosophila's lymph gland. Upon metamorphosis, specializedhemocyte subtypes are released from the lymph gland and carried over in afunctional state to the adult. In the absence of Wigglesworthia,GmmWgm− larvae producesignificantly less hemocytes than their WT counterparts. Several innate immunitypathways are activated upon inoculation of E. coli into thehemocoel of mature adult GmmWT. Tsetse'spreliminary line of defense against E. coli infection likelyinvolves melanization at the wound site. This process is initiated by localizedcrystal cells, which instigate the melanization cascade by secretingprophenoloxidase (PPO) into the hemolymph. Pathogens that circumvent the woundsite then encounter phagocyte-mediated cellular and humoral immune responses.Soluble TEPs likely opsonize bacterial cells, thus tagging them for engulfment byphagocytes. Lysis of engulfed bacteria causes the release of bacterialpeptidoglycan PGN that subsequently stimulates the production of AMPs by the fatbody. AMPs, which are also generated by hemocytes, are then secreted into thehemolymph where they further abrogate microbial proliferation. Hemocytes alsoproduce reactive oxygen intermediates, such as iNOS, that exhibit direct bacterialtoxicity and further stimulate humoral immunity. In the case ofGmmWgm− adults, incapacitatedhematopoiesis during larval stages results in severely compromised immunity thatrenders these flies highly susceptible as adults to bacterial infection.
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pbio-1000619-g006: Wigglesworthia modulates the development and function oftsetse's immune system.Through a currently unknown mechanism, the presence ofWigglesworthia in GmmWT larvaestimulates hemocyte differentiation in a specialized organ that is homologous toDrosophila's lymph gland. Upon metamorphosis, specializedhemocyte subtypes are released from the lymph gland and carried over in afunctional state to the adult. In the absence of Wigglesworthia,GmmWgm− larvae producesignificantly less hemocytes than their WT counterparts. Several innate immunitypathways are activated upon inoculation of E. coli into thehemocoel of mature adult GmmWT. Tsetse'spreliminary line of defense against E. coli infection likelyinvolves melanization at the wound site. This process is initiated by localizedcrystal cells, which instigate the melanization cascade by secretingprophenoloxidase (PPO) into the hemolymph. Pathogens that circumvent the woundsite then encounter phagocyte-mediated cellular and humoral immune responses.Soluble TEPs likely opsonize bacterial cells, thus tagging them for engulfment byphagocytes. Lysis of engulfed bacteria causes the release of bacterialpeptidoglycan PGN that subsequently stimulates the production of AMPs by the fatbody. AMPs, which are also generated by hemocytes, are then secreted into thehemolymph where they further abrogate microbial proliferation. Hemocytes alsoproduce reactive oxygen intermediates, such as iNOS, that exhibit direct bacterialtoxicity and further stimulate humoral immunity. In the case ofGmmWgm− adults, incapacitatedhematopoiesis during larval stages results in severely compromised immunity thatrenders these flies highly susceptible as adults to bacterial infection.

Mentions: In the present study we demonstrate that Wigglesworthia is intimatelyinvolved in regulating the maturation and function of tsetse's cellular immunesystem during immature larval development. We present a model that links the presence ofWigglesworthia in larval progeny with host immune system maturationduring development and the subsequent ability of adult tsetse to overcome infection withforeign microbes (Figure 6).Obligate symbioses between intracellular bacteria and multi-cellular eukaryotesrepresent millions of years of co-evolution during which time both partners have adaptedto increase each other's overall fitness. The association between tsetse andWigglesworthia is an example of this reciprocal relationship in thatneither organism can survive in the absence of the other.


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

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

Wigglesworthia modulates the development and function oftsetse's immune system.Through a currently unknown mechanism, the presence ofWigglesworthia in GmmWT larvaestimulates hemocyte differentiation in a specialized organ that is homologous toDrosophila's lymph gland. Upon metamorphosis, specializedhemocyte subtypes are released from the lymph gland and carried over in afunctional state to the adult. In the absence of Wigglesworthia,GmmWgm− larvae producesignificantly less hemocytes than their WT counterparts. Several innate immunitypathways are activated upon inoculation of E. coli into thehemocoel of mature adult GmmWT. Tsetse'spreliminary line of defense against E. coli infection likelyinvolves melanization at the wound site. This process is initiated by localizedcrystal cells, which instigate the melanization cascade by secretingprophenoloxidase (PPO) into the hemolymph. Pathogens that circumvent the woundsite then encounter phagocyte-mediated cellular and humoral immune responses.Soluble TEPs likely opsonize bacterial cells, thus tagging them for engulfment byphagocytes. Lysis of engulfed bacteria causes the release of bacterialpeptidoglycan PGN that subsequently stimulates the production of AMPs by the fatbody. AMPs, which are also generated by hemocytes, are then secreted into thehemolymph where they further abrogate microbial proliferation. Hemocytes alsoproduce reactive oxygen intermediates, such as iNOS, that exhibit direct bacterialtoxicity and further stimulate humoral immunity. In the case ofGmmWgm− adults, incapacitatedhematopoiesis during larval stages results in severely compromised immunity thatrenders these flies highly susceptible as adults to bacterial infection.
© Copyright Policy
Related In: Results  -  Collection

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

pbio-1000619-g006: Wigglesworthia modulates the development and function oftsetse's immune system.Through a currently unknown mechanism, the presence ofWigglesworthia in GmmWT larvaestimulates hemocyte differentiation in a specialized organ that is homologous toDrosophila's lymph gland. Upon metamorphosis, specializedhemocyte subtypes are released from the lymph gland and carried over in afunctional state to the adult. In the absence of Wigglesworthia,GmmWgm− larvae producesignificantly less hemocytes than their WT counterparts. Several innate immunitypathways are activated upon inoculation of E. coli into thehemocoel of mature adult GmmWT. Tsetse'spreliminary line of defense against E. coli infection likelyinvolves melanization at the wound site. This process is initiated by localizedcrystal cells, which instigate the melanization cascade by secretingprophenoloxidase (PPO) into the hemolymph. Pathogens that circumvent the woundsite then encounter phagocyte-mediated cellular and humoral immune responses.Soluble TEPs likely opsonize bacterial cells, thus tagging them for engulfment byphagocytes. Lysis of engulfed bacteria causes the release of bacterialpeptidoglycan PGN that subsequently stimulates the production of AMPs by the fatbody. AMPs, which are also generated by hemocytes, are then secreted into thehemolymph where they further abrogate microbial proliferation. Hemocytes alsoproduce reactive oxygen intermediates, such as iNOS, that exhibit direct bacterialtoxicity and further stimulate humoral immunity. In the case ofGmmWgm− adults, incapacitatedhematopoiesis during larval stages results in severely compromised immunity thatrenders these flies highly susceptible as adults to bacterial infection.
Mentions: In the present study we demonstrate that Wigglesworthia is intimatelyinvolved in regulating the maturation and function of tsetse's cellular immunesystem during immature larval development. We present a model that links the presence ofWigglesworthia in larval progeny with host immune system maturationduring development and the subsequent ability of adult tsetse to overcome infection withforeign microbes (Figure 6).Obligate symbioses between intracellular bacteria and multi-cellular eukaryotesrepresent millions of years of co-evolution during which time both partners have adaptedto increase each other's overall fitness. The association between tsetse andWigglesworthia is an example of this reciprocal relationship in thatneither organism can survive in the absence of the other.

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