title: Essential role of neutrophils but not mammary alveolar macrophages in a murine model of acute Escherichia coli mastitis.
abstract: Mastitis, the inflammation of the mammary gland, is an important disease affecting dairy animals worldwide. The disease is caused by mammary pathogenic bacteria and Escherichia coli are frequently implicated. Virulence factors of mammary pathogenic E. coli are only partially known and intramammary challenge with LPS elicits neutrophil recruitment in experimental bovine and murine mastitis models. We have previously shown that neutrophil recruitment in LPS-induced murine mastitis is strictly dependent on mammary alveolar macrophages. However, the relative role of alveolar macrophages and blood neutrophils in E. coli mastitis is not well defined. To this end, we selectively depleted mammary alveolar macrophages or blood neutrophils before intramammary challenge with E. coli strain P4 (ECP4). Mice depleted of alveolar macrophages prior to intramammary challenge recruited neutrophils normally and restricted bacterial growth and interstitial invasion. Importantly however, upon depletion of alveolar macrophages, ECP4 invaded the mammary alveolar epithelial cells and formed intracellular bacterial communities. In contrast, neutrophil depletion prior to intramammary infection with ECP4 was associated with unrestricted bacterial growth, tissue damage, severe sepsis and mortality. This study suggests that neutrophils but not alveolar macrophages provide essential antimicrobial defense against mammary pathogenic E. coli. Furthermore, we show here similar invasion after depletion of alveolar macrophages as in our previous studies showing that LPS/TLR4 signaling on alveolar macrophages abrogates ECP4 invasion of the mammary epithelium. Interestingly, similar ECP4 invasion and formation of intracellular communities were also observed following intramammary infection of either iNOS gene-deficient or IL-1 receptor type 1 gene-deficient mice.
authors.affiliation: The Koret School of Veterinary Medicine, Faculty of Agriculture, The Hebrew University of Jerusalem, POB 12, Rehovot 76100, Israel.
authors.forename: Sharon
authors.initials: S
authors.lastname: Elazar
authors.forename: Erez
authors.initials: E
authors.lastname: Gonen
authors.forename: Ayala
authors.initials: A
authors.lastname: Livneh-Kol
authors.forename: Ilan
authors.initials: I
authors.lastname: Rosenshine
authors.forename: Nahum Y
authors.initials: NY
authors.lastname: Shpigel
mesh_terms: D000818:Animals; D004926:Escherichia coli / Q000145:classification; D004927:Escherichia coli Infections / Q000276:immunology* / Q000382:microbiology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000502:physiology*; D008321:Mammary Glands, Animal / Q000166:cytology*; D008413:Mastitis / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D018345:Mice, Knockout; D009504:Neutrophils / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D017472:Receptors, Interleukin-1; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; D052247:Nitric Oxide Synthase Type II