title: Increased susceptibility of melanin-concentrating hormone-deficient mice to infection with Salmonella enterica serovar Typhimurium.
abstract: Melanin-concentrating hormone (MCH) was initially identified in mammals as a hypothalamic neuropeptide regulating appetite and energy balance. However, the wide distribution of MCH receptors in peripheral tissues suggests additional functions for MCH which remain largely unknown. We have previously reported that mice lacking MCH develop attenuated intestinal inflammation when exposed to Clostridium difficile toxin A. To further characterize the role of MCH in host defense mechanisms against intestinal pathogens, Salmonella enterocolitis (using Salmonella enterica serovar Typhimurium) was induced in MCH-deficient mice and their wild-type littermates. In the absence of MCH, infected mice had increased mortality associated with higher bacterial loads in blood, liver, and spleen. Moreover, the knockout mice developed more-severe intestinal inflammation, based on epithelial damage, immune cell infiltrates, and local and systemic cytokine levels. Paradoxically, these enhanced inflammatory responses in the MCH knockout mice were associated with disproportionally lower levels of macrophages infiltrating the intestine. Hence, we investigated potential direct effects of MCH on monocyte/macrophage functions critical for defense against intestinal pathogens. Using RAW 264.7 mouse monocytic cells, which express endogenous MCH receptor, we found that treatment with MCH enhanced the phagocytic capacity of these cells. Taken together, these findings reveal a previously unappreciated role for MCH in host-bacterial interactions.
authors.affiliation: Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Apostolos K A
authors.initials: AK
authors.lastname: Karagiannis
authors.forename: Dimitrios C
authors.initials: DC
authors.lastname: Ziogas
authors.forename: Beatriz
authors.initials: B
authors.lastname: Gras-Miralles
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Geiger
authors.forename: Jutta
authors.initials: J
authors.lastname: Nagel
authors.forename: Estela
authors.initials: E
authors.lastname: Trebicka
authors.forename: Robert
authors.initials: R
authors.lastname: Najarian
authors.forename: Bobby J
authors.initials: BJ
authors.lastname: Cherayil
authors.forename: Efi
authors.initials: E
authors.lastname: Kokkotou
mesh_terms: D000818:Animals; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004198:Disease Susceptibility / Q000276:immunology; D007028:Hypothalamic Hormones / Q000276:immunology* / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology / Q000382:microbiology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D008297:Male; D008543:Melanins / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D010587:Phagocytosis / Q000276:immunology; D010907:Pituitary Hormones / Q000276:immunology* / Q000378:metabolism*; D017481:Receptors, Somatostatin / Q000276:immunology / Q000378:metabolism; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000378:metabolism* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000276:immunology*
chemical_list: D016207:Cytokines; D007028:Hypothalamic Hormones; C491209:Mchr1 protein, mouse; D008543:Melanins; D010907:Pituitary Hormones; D017481:Receptors, Somatostatin; C019463:melanin-concentrating hormone