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Involvement of skeletal muscle gene regulatory network in susceptibility to wound infection following trauma.

Apidianakis Y, Mindrinos MN, Xiao W, Tegos GP, Papisov MI, Hamblin MR, Davis RW, Tompkins RG, Rahme LG - PLoS ONE (2007)

Bottom Line: Despite recent advances in our understanding the pathophysiology of trauma, the basis of the predisposition of trauma patients to infection remains unclear.Our study links SMG expression and function to increased susceptibility to infection, and suggests that P. aeruginosa affects SMG homeostasis locally by restricting SMG expression in injured skeletal muscle tissue.Local potentiation of these host responses, and/or inhibition of their suppression by virulent P. aeruginosa cells, could lead to novel therapies that prevent or treat deleterious and potentially fatal infections in severely injured individuals.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, United States of America.

ABSTRACT
Despite recent advances in our understanding the pathophysiology of trauma, the basis of the predisposition of trauma patients to infection remains unclear. A Drosophila melanogaster/Pseudomonas aeruginosa injury and infection model was used to identify host genetic components that contribute to the hyper-susceptibility to infection that follows severe trauma. We show that P. aeruginosa compromises skeletal muscle gene (SMG) expression at the injury site to promote infection. We demonstrate that activation of SMG structural components is under the control of cJun-N-terminal Kinase (JNK) Kinase, Hemipterous (Hep), and activation of this pathway promotes local resistance to P. aeruginosa in flies and mice. Our study links SMG expression and function to increased susceptibility to infection, and suggests that P. aeruginosa affects SMG homeostasis locally by restricting SMG expression in injured skeletal muscle tissue. Local potentiation of these host responses, and/or inhibition of their suppression by virulent P. aeruginosa cells, could lead to novel therapies that prevent or treat deleterious and potentially fatal infections in severely injured individuals.

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Skeletal muscle structural gene function contributes to host hypersusceptibility to infection.Survival kinetics of mutants for the flight muscle genes act88F, hdp, or Tm2 following local PA14 infection of the thorax (A) or the abdomen (B) relative to wild-type flies. Detailed statistical evaluations of the survival kinetics are presented in Table S2.
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pone-0001356-g002: Skeletal muscle structural gene function contributes to host hypersusceptibility to infection.Survival kinetics of mutants for the flight muscle genes act88F, hdp, or Tm2 following local PA14 infection of the thorax (A) or the abdomen (B) relative to wild-type flies. Detailed statistical evaluations of the survival kinetics are presented in Table S2.

Mentions: What does decrease SMG expression mean to the fly? For instance, does it promote host susceptibility to bacterial infection, and how; and is it local or systemic? Survival kinetics of the act88F, Tm2, and hdp mutant flies, defective in muscle structure and function [20], succumbed significantly earlier to thoracic PA14 infection than wild-type flies (Fig. 2A and SI Table S2). This increased susceptibility was local and thorax specific, as the survival kinetics of abdominally injured and infected wild-type and mutant flies did not differ (Fig. 2B and Table S2). Moreover, no (or only negligible) SMG upregulation was observed with abdominal infection (Fig. 1E), as SMG expression in flies that were abdominally injured and inoculated with CF5 or PA14 was similar to that in mock-inoculated and naïve flies. These results further confirm that SMG upregulation is thorax-specific (compare Figure 1A–D to 1E), and suggest that SMGs affect local muscular susceptibility to infection.


Involvement of skeletal muscle gene regulatory network in susceptibility to wound infection following trauma.

Apidianakis Y, Mindrinos MN, Xiao W, Tegos GP, Papisov MI, Hamblin MR, Davis RW, Tompkins RG, Rahme LG - PLoS ONE (2007)

Skeletal muscle structural gene function contributes to host hypersusceptibility to infection.Survival kinetics of mutants for the flight muscle genes act88F, hdp, or Tm2 following local PA14 infection of the thorax (A) or the abdomen (B) relative to wild-type flies. Detailed statistical evaluations of the survival kinetics are presented in Table S2.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2131783&req=5

pone-0001356-g002: Skeletal muscle structural gene function contributes to host hypersusceptibility to infection.Survival kinetics of mutants for the flight muscle genes act88F, hdp, or Tm2 following local PA14 infection of the thorax (A) or the abdomen (B) relative to wild-type flies. Detailed statistical evaluations of the survival kinetics are presented in Table S2.
Mentions: What does decrease SMG expression mean to the fly? For instance, does it promote host susceptibility to bacterial infection, and how; and is it local or systemic? Survival kinetics of the act88F, Tm2, and hdp mutant flies, defective in muscle structure and function [20], succumbed significantly earlier to thoracic PA14 infection than wild-type flies (Fig. 2A and SI Table S2). This increased susceptibility was local and thorax specific, as the survival kinetics of abdominally injured and infected wild-type and mutant flies did not differ (Fig. 2B and Table S2). Moreover, no (or only negligible) SMG upregulation was observed with abdominal infection (Fig. 1E), as SMG expression in flies that were abdominally injured and inoculated with CF5 or PA14 was similar to that in mock-inoculated and naïve flies. These results further confirm that SMG upregulation is thorax-specific (compare Figure 1A–D to 1E), and suggest that SMGs affect local muscular susceptibility to infection.

Bottom Line: Despite recent advances in our understanding the pathophysiology of trauma, the basis of the predisposition of trauma patients to infection remains unclear.Our study links SMG expression and function to increased susceptibility to infection, and suggests that P. aeruginosa affects SMG homeostasis locally by restricting SMG expression in injured skeletal muscle tissue.Local potentiation of these host responses, and/or inhibition of their suppression by virulent P. aeruginosa cells, could lead to novel therapies that prevent or treat deleterious and potentially fatal infections in severely injured individuals.

View Article: PubMed Central - PubMed

Affiliation: Department of Surgery, Harvard Medical School and Massachusetts General Hospital, Boston, Massachusetts, United States of America.

ABSTRACT
Despite recent advances in our understanding the pathophysiology of trauma, the basis of the predisposition of trauma patients to infection remains unclear. A Drosophila melanogaster/Pseudomonas aeruginosa injury and infection model was used to identify host genetic components that contribute to the hyper-susceptibility to infection that follows severe trauma. We show that P. aeruginosa compromises skeletal muscle gene (SMG) expression at the injury site to promote infection. We demonstrate that activation of SMG structural components is under the control of cJun-N-terminal Kinase (JNK) Kinase, Hemipterous (Hep), and activation of this pathway promotes local resistance to P. aeruginosa in flies and mice. Our study links SMG expression and function to increased susceptibility to infection, and suggests that P. aeruginosa affects SMG homeostasis locally by restricting SMG expression in injured skeletal muscle tissue. Local potentiation of these host responses, and/or inhibition of their suppression by virulent P. aeruginosa cells, could lead to novel therapies that prevent or treat deleterious and potentially fatal infections in severely injured individuals.

Show MeSH
Related in: MedlinePlus