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

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          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.

          Abstract

          Summary: Using fruit fly and zebrafish models, we show that skeletal muscles are immune responsive tissues; they mount innate immune responses during bacterial infection – an evolutionarily conserved defense mechanism.

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          Most cited references43

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          Drosophila host defense: differential induction of antimicrobial peptide genes after infection by various classes of microorganisms.

          Insects respond to microbial infection by the rapid and transient expression of several genes encoding potent antimicrobial peptides. Herein we demonstrate that this antimicrobial response of Drosophila is not aspecific but can discriminate between various classes of microorganisms. We first observe that the genes encoding antibacterial and antifungal peptides are differentially expressed after injection of distinct microorganisms. More strikingly, Drosophila that are naturally infected by entomopathogenic fungi exhibit an adapted response by producing only peptides with antifungal activities. This response is mediated through the selective activation of the Toll pathway.
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            Tissue-specific inducible expression of antimicrobial peptide genes in Drosophila surface epithelia.

            The production of antimicrobial peptides is an important aspect of host defense in multicellular organisms. In Drosophila, seven antimicrobial peptides with different spectra of activities are synthesized by the fat body during the immune response and secreted into the hemolymph. Using GFP reporter transgenes, we show here that all seven Drosophila antimicrobial peptides can be induced in surface epithelia in a tissue-specific manner. The imd gene plays a critical role in the activation of this local response to infection. In particular, drosomycin expression, which is regulated by the Toll pathway during the systemic response, is regulated by imd in the respiratory tract, thus demonstrating the existence of distinct regulatory mechanisms for local and systemic induction of antimicrobial peptide genes in Drosophila.
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              Reactive Oxygen Species in Skeletal Muscle Signaling

              Generation of reactive oxygen species (ROS) is a ubiquitous phenomenon in eukaryotic cells' life. Up to the 1990s of the past century, ROS have been solely considered as toxic species resulting in oxidative stress, pathogenesis and aging. However, there is now clear evidence that ROS are not merely toxic species but also—within certain concentrations—useful signaling molecules regulating physiological processes. During intense skeletal muscle contractile activity myotubes' mitochondria generate high ROS flows: this renders skeletal muscle a tissue where ROS hold a particular relevance. According to their hormetic nature, in muscles ROS may trigger different signaling pathways leading to diverging responses, from adaptation to cell death. Whether a “positive” or “negative” response will prevail depends on many variables such as, among others, the site of ROS production, the persistence of ROS flow or target cells' antioxidant status. In this light, a specific threshold of physiological ROS concentrations above which ROS exert negative, toxic effects is hard to determine, and the concept of “physiologically compatible” levels of ROS would better fit with such a dynamic scenario. In this review these concepts will be discussed along with the most relevant signaling pathways triggered and/or affected by ROS in skeletal muscle.
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                Author and article information

                Journal
                Dis Model Mech
                Dis Model Mech
                DMM
                dmm
                Disease Models & Mechanisms
                The Company of Biologists Ltd
                1754-8403
                1754-8411
                1 June 2016
                1 June 2016
                : 9
                : 6
                : 697-705
                Affiliations
                Department of Molecular Reproduction, Development and Genetics, Indian Institute of Science , Bangalore 560012, India
                Author notes
                Author information
                http://orcid.org/0000-0002-0616-5995
                Article
                DMM022665
                10.1242/dmm.022665
                4920145
                27101844
                782cc425-ee1b-434c-bba4-76d96a345bb4
                © 2016. Published by The Company of Biologists Ltd

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.

                History
                : 9 August 2015
                : 18 April 2016
                Funding
                Funded by: Indian Institute of Science, http://dx.doi.org/10.13039/100007780;
                Funded by: Department of Biotechnology, Ministry of Science and Technology, http://dx.doi.org/10.13039/501100001407;
                Funded by: Council of Scientific and Industrial Research, Ministry of Human Resource Development, http://dx.doi.org/10.13039/501100001412;
                Funded by: University Grants Commission, http://dx.doi.org/10.13039/501100001501;
                Categories
                Dros
                Zebra
                Research Article

                Molecular medicine
                muscle,drosophila,zebrafish,infection,immunity,anti-microbial peptides
                Molecular medicine
                muscle, drosophila, zebrafish, infection, immunity, anti-microbial peptides

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