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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.

No MeSH data available.


Related in: MedlinePlus

IFM mutants are susceptible to bacterial infection. (A) Hematoxylin-stained hemithoraces of the fly strains used in the study, alongside a representative schematic, show a spectrum of defects in the IFMs. CS: the wild-type fly strain Canton-S. (B,C) Survival curves of the muscle mutants post-infection with (B) Salmonella and (C) Bacillus subtilis by septic injury. A log-rank test was done for estimating the significance of the survival curves. (B) Salmonella infected versus uninfected: Canton-S, P=0.0094; up1, P=0.0034; up101, P<0.0001; hdp2, P<0.0001; hdp3, P<0.0001; TM23, P=0.0006; Act88FKM88, P<0.0001. Mutant versus wild type: up1, P=0.1171; up101, P<0.0001; hdp2, P<0.0001; hdp3, P<0.0001; TM23, P=0.0364; Act88FKM88, P<0.0001. (C) Bacillus infected versus uninfected: All fly strains, P<0.0001. Mutant versus wild type: up1, P=0.0139; up101, P=0.0002; hdp2, P=0.0346; hdp3, <0.0001; TM23, P=0.1646; Act88FKM88, P=0.0009. n>80. Open circles, IFM-specific mutants; dashed lines, uninfected controls; U, uninfected; I, infected; dpi, days post-infection; hpi, hours post-infection.
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DMM022665F1: IFM mutants are susceptible to bacterial infection. (A) Hematoxylin-stained hemithoraces of the fly strains used in the study, alongside a representative schematic, show a spectrum of defects in the IFMs. CS: the wild-type fly strain Canton-S. (B,C) Survival curves of the muscle mutants post-infection with (B) Salmonella and (C) Bacillus subtilis by septic injury. A log-rank test was done for estimating the significance of the survival curves. (B) Salmonella infected versus uninfected: Canton-S, P=0.0094; up1, P=0.0034; up101, P<0.0001; hdp2, P<0.0001; hdp3, P<0.0001; TM23, P=0.0006; Act88FKM88, P<0.0001. Mutant versus wild type: up1, P=0.1171; up101, P<0.0001; hdp2, P<0.0001; hdp3, P<0.0001; TM23, P=0.0364; Act88FKM88, P<0.0001. (C) Bacillus infected versus uninfected: All fly strains, P<0.0001. Mutant versus wild type: up1, P=0.0139; up101, P=0.0002; hdp2, P=0.0346; hdp3, <0.0001; TM23, P=0.1646; Act88FKM88, P=0.0009. n>80. Open circles, IFM-specific mutants; dashed lines, uninfected controls; U, uninfected; I, infected; dpi, days post-infection; hpi, hours post-infection.

Mentions: Mutants of Drosophila muscle structural genes were selected for the study. Being flightless, these mutants could not be distinguished at the functional level (Fig. S1D); however, at the structural level, they showed defects of the IFMs that varied through a spectrum amongst the mutants (Fig. 1A). Most mutants showed hypercontraction (up1, up101, wupAhdp−2, wupAhdp−3) (Nongthomba et al., 2003, 2004, 2007), hypomorph for Tropomyosin Tm23 resembled the wild type in IFM morphology despite being flightless, IFM-specific actin- Act88FKM88 had a wavy appearance of the IFMs, and IFM-specific Troponin I- wupAhdp−3 had the most severely affected IFMs with no muscles (Fig. 1A).Fig. 1.


Muscles provide protection during microbial infection by activating innate immune response pathways in Drosophila and zebrafish
IFM mutants are susceptible to bacterial infection. (A) Hematoxylin-stained hemithoraces of the fly strains used in the study, alongside a representative schematic, show a spectrum of defects in the IFMs. CS: the wild-type fly strain Canton-S. (B,C) Survival curves of the muscle mutants post-infection with (B) Salmonella and (C) Bacillus subtilis by septic injury. A log-rank test was done for estimating the significance of the survival curves. (B) Salmonella infected versus uninfected: Canton-S, P=0.0094; up1, P=0.0034; up101, P<0.0001; hdp2, P<0.0001; hdp3, P<0.0001; TM23, P=0.0006; Act88FKM88, P<0.0001. Mutant versus wild type: up1, P=0.1171; up101, P<0.0001; hdp2, P<0.0001; hdp3, P<0.0001; TM23, P=0.0364; Act88FKM88, P<0.0001. (C) Bacillus infected versus uninfected: All fly strains, P<0.0001. Mutant versus wild type: up1, P=0.0139; up101, P=0.0002; hdp2, P=0.0346; hdp3, <0.0001; TM23, P=0.1646; Act88FKM88, P=0.0009. n>80. Open circles, IFM-specific mutants; dashed lines, uninfected controls; U, uninfected; I, infected; dpi, days post-infection; hpi, hours post-infection.
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DMM022665F1: IFM mutants are susceptible to bacterial infection. (A) Hematoxylin-stained hemithoraces of the fly strains used in the study, alongside a representative schematic, show a spectrum of defects in the IFMs. CS: the wild-type fly strain Canton-S. (B,C) Survival curves of the muscle mutants post-infection with (B) Salmonella and (C) Bacillus subtilis by septic injury. A log-rank test was done for estimating the significance of the survival curves. (B) Salmonella infected versus uninfected: Canton-S, P=0.0094; up1, P=0.0034; up101, P<0.0001; hdp2, P<0.0001; hdp3, P<0.0001; TM23, P=0.0006; Act88FKM88, P<0.0001. Mutant versus wild type: up1, P=0.1171; up101, P<0.0001; hdp2, P<0.0001; hdp3, P<0.0001; TM23, P=0.0364; Act88FKM88, P<0.0001. (C) Bacillus infected versus uninfected: All fly strains, P<0.0001. Mutant versus wild type: up1, P=0.0139; up101, P=0.0002; hdp2, P=0.0346; hdp3, <0.0001; TM23, P=0.1646; Act88FKM88, P=0.0009. n>80. Open circles, IFM-specific mutants; dashed lines, uninfected controls; U, uninfected; I, infected; dpi, days post-infection; hpi, hours post-infection.
Mentions: Mutants of Drosophila muscle structural genes were selected for the study. Being flightless, these mutants could not be distinguished at the functional level (Fig. S1D); however, at the structural level, they showed defects of the IFMs that varied through a spectrum amongst the mutants (Fig. 1A). Most mutants showed hypercontraction (up1, up101, wupAhdp−2, wupAhdp−3) (Nongthomba et al., 2003, 2004, 2007), hypomorph for Tropomyosin Tm23 resembled the wild type in IFM morphology despite being flightless, IFM-specific actin- Act88FKM88 had a wavy appearance of the IFMs, and IFM-specific Troponin I- wupAhdp−3 had the most severely affected IFMs with no muscles (Fig. 1A).Fig. 1.

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