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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 the expression of immunity-related genesin adult tsetse.(A) Target gene expression in uninfected GmmWT andGmmWgm− adults is indicatedrelative to the constitutively expressed tsetse β-tubulin gene. (B)Fold-change in the expression of immunity-related genes inGmmWT andGmmWgm− tsetse 3 dpi withE. coli K12. All values for both tsetse strains arerepresented as a fraction of average normalized gene expression levels inbacteria-infected flies relative to expression levels in PBS-injected controls.In (A) and (B), quantitative measurements were performed on three biologicalsamples in duplicate. Values are represented as means (±SEM). *p<0.05, ** p<0.005(Student's t-test).
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pbio-1000619-g002: The effect of symbiont status on the expression of immunity-related genesin adult tsetse.(A) Target gene expression in uninfected GmmWT andGmmWgm− adults is indicatedrelative to the constitutively expressed tsetse β-tubulin gene. (B)Fold-change in the expression of immunity-related genes inGmmWT andGmmWgm− tsetse 3 dpi withE. coli K12. All values for both tsetse strains arerepresented as a fraction of average normalized gene expression levels inbacteria-infected flies relative to expression levels in PBS-injected controls.In (A) and (B), quantitative measurements were performed on three biologicalsamples in duplicate. Values are represented as means (±SEM). *p<0.05, ** p<0.005(Student's t-test).

Mentions: Our expression results indicate that symbiont status plays little or no role in theexpression of immunity-related genes in uninfected adults. In fact, with theexception of the AMP defensin, no significant differences inimmunity-related gene expression between mature uninfectedGmmWT andGmmWgm− adults (Figure 2A). However, we observed a considerablydifferent profile of immunity-related gene expression when these different flystrains were infected with E. coli K12. Under these circumstances,all of the genes evaluated (with the exception of defensin) were expressed atsignificantly higher levels in GmmWT compared toGmmWgm− individuals (Figure 2B). Particular striking wasthe fact that the induction of pathways associated with cellular immunity, such aspathogen recognition (tep2 and tep4) andmelanization (PPO), were significantly compromised in matureGmmWgm− adults. The absence of arobust cellular immune response is likely the cause of high mortality among theseindividuals following E. coli infection. This analysis indicatesthat Wigglesworthia must be present during the development ofimmature tsetse in order for immune-related genes to subsequently be expressed inmature E. coli–infected adults.


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 the expression of immunity-related genesin adult tsetse.(A) Target gene expression in uninfected GmmWT andGmmWgm− adults is indicatedrelative to the constitutively expressed tsetse β-tubulin gene. (B)Fold-change in the expression of immunity-related genes inGmmWT andGmmWgm− tsetse 3 dpi withE. coli K12. All values for both tsetse strains arerepresented as a fraction of average normalized gene expression levels inbacteria-infected flies relative to expression levels in PBS-injected controls.In (A) and (B), quantitative measurements were performed on three biologicalsamples in duplicate. Values are represented as means (±SEM). *p<0.05, ** p<0.005(Student's t-test).
© Copyright Policy
Related In: Results  -  Collection

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

pbio-1000619-g002: The effect of symbiont status on the expression of immunity-related genesin adult tsetse.(A) Target gene expression in uninfected GmmWT andGmmWgm− adults is indicatedrelative to the constitutively expressed tsetse β-tubulin gene. (B)Fold-change in the expression of immunity-related genes inGmmWT andGmmWgm− tsetse 3 dpi withE. coli K12. All values for both tsetse strains arerepresented as a fraction of average normalized gene expression levels inbacteria-infected flies relative to expression levels in PBS-injected controls.In (A) and (B), quantitative measurements were performed on three biologicalsamples in duplicate. Values are represented as means (±SEM). *p<0.05, ** p<0.005(Student's t-test).
Mentions: Our expression results indicate that symbiont status plays little or no role in theexpression of immunity-related genes in uninfected adults. In fact, with theexception of the AMP defensin, no significant differences inimmunity-related gene expression between mature uninfectedGmmWT andGmmWgm− adults (Figure 2A). However, we observed a considerablydifferent profile of immunity-related gene expression when these different flystrains were infected with E. coli K12. Under these circumstances,all of the genes evaluated (with the exception of defensin) were expressed atsignificantly higher levels in GmmWT compared toGmmWgm− individuals (Figure 2B). Particular striking wasthe fact that the induction of pathways associated with cellular immunity, such aspathogen recognition (tep2 and tep4) andmelanization (PPO), were significantly compromised in matureGmmWgm− adults. The absence of arobust cellular immune response is likely the cause of high mortality among theseindividuals following E. coli infection. This analysis indicatesthat Wigglesworthia must be present during the development ofimmature tsetse in order for immune-related genes to subsequently be expressed inmature E. coli–infected adults.

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