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Muscles provide protection during microbial infection by activating innate immune response pathways in Drosophila and zebrafish

View Article: PubMed Central - PubMed

ABSTRACT

Muscle contraction brings about movement and locomotion in animals. However, muscles have also been implicated in several atypical physiological processes including immune response. The role of muscles in immunity and the mechanism involved has not yet been deciphered. In this paper, using Drosophila indirect flight muscles (IFMs) as a model, we show that muscles are immune-responsive tissues. Flies with defective IFMs are incapable of mounting a potent humoral immune response. Upon immune challenge, the IFMs produce anti-microbial peptides (AMPs) through the activation of canonical signaling pathways, and these IFM-synthesized AMPs are essential for survival upon infection. The trunk muscles of zebrafish, a vertebrate model system, also possess the capacity to mount an immune response against bacterial infections, thus establishing that immune responsiveness of muscles is evolutionarily conserved. Our results suggest that physiologically fit muscles might boost the innate immune response of an individual.

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Induction of AMPs in muscle mutants upon infection is sub-optimal. (A,B) qRT-PCR analyses for estimation of induction of gene expression for anti-microbial peptides (A) Drosocin and (B) Cecropin upon infection. The mRNA was extracted from whole flies 6 h after infection with Salmonella. The values represented are mean±s.e.m. of three independent replicates. *, significant difference in expression of infected versus uninfected; #, significant difference in induction levels of infected mutant versus infected wild type. ns, P>0.05; */#, P<0.05; **/##, P<0.001; ***/###, P<0.0001. CS, the wild-type fly strain Canton-S; u, uninfected; i, infected.
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DMM022665F2: Induction of AMPs in muscle mutants upon infection is sub-optimal. (A,B) qRT-PCR analyses for estimation of induction of gene expression for anti-microbial peptides (A) Drosocin and (B) Cecropin upon infection. The mRNA was extracted from whole flies 6 h after infection with Salmonella. The values represented are mean±s.e.m. of three independent replicates. *, significant difference in expression of infected versus uninfected; #, significant difference in induction levels of infected mutant versus infected wild type. ns, P>0.05; */#, P<0.05; **/##, P<0.001; ***/###, P<0.0001. CS, the wild-type fly strain Canton-S; u, uninfected; i, infected.

Mentions: Upon bacterial infection, the Drosophila innate immune system induces the expression of a specific set of AMPs directed against the infecting bacteria by primarily activating either the Toll or the immune deficiency (Imd) pathway (Lemaitre et al., 1997). Cecropin and Drosocin, two AMPs downstream of the Imd pathway, show a substantial increase in their expression six hours post-infection with Salmonella (Fig. 2A,B). In most muscle mutants, AMPs induction was diminished compared with wild-type flies post-infection (Fig. 2A,B); although basal expression of AMPs was comparable to that of naïve wild-type flies (Fig. S3A). wupAhdp−3 flies demonstrated the weakest response to infection with no induction of either AMP. In Tm23 flies, increases in expression of both the AMPs were comparable to wild type (Fig. 2A,B), and AMP induction in the other mutants was moderate. As would be expected, reduced AMP induction correlated well with both reduced infection survival (Figs 1, 2; n=28, Spearman r=0.607, P=0.0006) and the degree of IFM defect (Fig. 2; Fig. S2; n=14, Spearman r=0.847, P=0.0001).Fig. 2.


Muscles provide protection during microbial infection by activating innate immune response pathways in Drosophila and zebrafish
Induction of AMPs in muscle mutants upon infection is sub-optimal. (A,B) qRT-PCR analyses for estimation of induction of gene expression for anti-microbial peptides (A) Drosocin and (B) Cecropin upon infection. The mRNA was extracted from whole flies 6 h after infection with Salmonella. The values represented are mean±s.e.m. of three independent replicates. *, significant difference in expression of infected versus uninfected; #, significant difference in induction levels of infected mutant versus infected wild type. ns, P>0.05; */#, P<0.05; **/##, P<0.001; ***/###, P<0.0001. CS, the wild-type fly strain Canton-S; u, uninfected; i, infected.
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4920145&req=5

DMM022665F2: Induction of AMPs in muscle mutants upon infection is sub-optimal. (A,B) qRT-PCR analyses for estimation of induction of gene expression for anti-microbial peptides (A) Drosocin and (B) Cecropin upon infection. The mRNA was extracted from whole flies 6 h after infection with Salmonella. The values represented are mean±s.e.m. of three independent replicates. *, significant difference in expression of infected versus uninfected; #, significant difference in induction levels of infected mutant versus infected wild type. ns, P>0.05; */#, P<0.05; **/##, P<0.001; ***/###, P<0.0001. CS, the wild-type fly strain Canton-S; u, uninfected; i, infected.
Mentions: Upon bacterial infection, the Drosophila innate immune system induces the expression of a specific set of AMPs directed against the infecting bacteria by primarily activating either the Toll or the immune deficiency (Imd) pathway (Lemaitre et al., 1997). Cecropin and Drosocin, two AMPs downstream of the Imd pathway, show a substantial increase in their expression six hours post-infection with Salmonella (Fig. 2A,B). In most muscle mutants, AMPs induction was diminished compared with wild-type flies post-infection (Fig. 2A,B); although basal expression of AMPs was comparable to that of naïve wild-type flies (Fig. S3A). wupAhdp−3 flies demonstrated the weakest response to infection with no induction of either AMP. In Tm23 flies, increases in expression of both the AMPs were comparable to wild type (Fig. 2A,B), and AMP induction in the other mutants was moderate. As would be expected, reduced AMP induction correlated well with both reduced infection survival (Figs 1, 2; n=28, Spearman r=0.607, P=0.0006) and the degree of IFM defect (Fig. 2; Fig. S2; n=14, Spearman r=0.847, P=0.0001).Fig. 2.

View Article: PubMed Central - PubMed

ABSTRACT

Muscle contraction brings about movement and locomotion in animals. However, muscles have also been implicated in several atypical physiological processes including immune response. The role of muscles in immunity and the mechanism involved has not yet been deciphered. In this paper, using Drosophila indirect flight muscles (IFMs) as a model, we show that muscles are immune-responsive tissues. Flies with defective IFMs are incapable of mounting a potent humoral immune response. Upon immune challenge, the IFMs produce anti-microbial peptides (AMPs) through the activation of canonical signaling pathways, and these IFM-synthesized AMPs are essential for survival upon infection. The trunk muscles of zebrafish, a vertebrate model system, also possess the capacity to mount an immune response against bacterial infections, thus establishing that immune responsiveness of muscles is evolutionarily conserved. Our results suggest that physiologically fit muscles might boost the innate immune response of an individual.

No MeSH data available.


Related in: MedlinePlus