Cytokines and neutrophil extracellular traps in the equine endometrium: friends or foes?

Abstract

SummaryCytokines may play a dual role in the reproductive tract -either involved in physiologic processes or mediating inflammation and other pathologic processes. Physiologic secretory and angiogenic function in the equine endometrium appears to be regulated by cytokines TNFa, FasL, IFNg through their receptors. These receptors are present in glandular epithelium, and stroma cells and their mRNA expression changes throughout the estrous cycle. Besides, interleukins (IL-1a and IL-1b) and their receptors mRNA expression vary according to various degrees of endometrium inflammation (endometritis) and fibrosis (endometrosis). A novel paradigm in innate immunity and neutrophils (PMN) hyperactivation is PMN ability to cast out their DNA in response to infectious stimuli. These PMN extracellular traps (NETs) bind and kill pathogens, at the infection site. The intriguing dilemma is that even though NETs may function as a first line of defense, they also release molecules that may contribute to tissue damage. Thus, we postulate that PMN present in the endometrium at estrus, mating or infection, might form NETs, and release nucleic and cytoplasmic proteins with immunomodulatory properties. Equine PMN stimulated in vitro showed NETs formation capacity when in contact with some bacteria strains obtained from mares with endometritis, such as Streptococcus zooepidemicus, Escherichia coli and Staphylococus capitis. In this regard, even though NETs and cytokines function as an effective antimicrobial first line of defense or modulate physiologic endometrial function, respectively (friends), they may also be involved in endometrial fibrosis pathogenesis and endometrial secretory function impairment, due to enhanced NETs formation and/or a decrease on NETs degradation (foes).Keywords: Neutrophil extracellular traps; cytokines, mare, endometrium, endometritis, reproductionZytokine und "neutrophile extrazelluläre Fallen" im Endometrium des Pferdes -Freund oder Feind?Zytokine können im Reproduktionstrakt in zweifacher Hinsicht eine Rolle spielen: zum einen sind sie an physiologischen Prozessen beteiligt, zum anderen vermitteln sie bei Entzündungen oder anderen Alterationen. Die equine endometriale physiologische sekretorische und angiogene Funktion scheint durch die Zytokine TNFa, FasL, IFNg durch ihre Rezeptoren reguliert zu werden. Diese sind in den glandulären Epithelien und den Stromazellen lokalisiert, ihre mRNA Expression ist innerhalb des Zyklusgeschehens veränderlich. Darüber hinaus variieren die Interleukine (IL-1a und IL-1b) und ihre Rezeptor-mRNA-Expression in Abhängigkeit vom Grad der Endometritis und Endometrose (periglanduläre Fibrose). Ein neues Denkmodell bezüglich der angeborenen Immunität und der Hyperaktivität der neutrophilen Granulozyten (PMN) ist die Ausschüttung ihrer DNA als Reaktion auf einen infektiösen Stimulus. Diese neutrophil extracelluar traps -"Neutrophile extrazelluläre Fallen", NETs, binden und töten pathogene Keime, im Falle einer Infektion. Das faszinierende Dilemma dabei ist, dass obwohl NETs ih...

Association of neutrophil morphology with bacterial isolates in equine tracheal wash samples

“…The nuclear lysis seen cytologically in these airway samples and classified as degenerate neutrophilia has a strong cytological resemblance to neutrophil extracellular traps (NETs, netosis), a mechanism by which neutrophils actively degenerate and release chromatin and associated antimicrobial molecules to trap and kill microbes [21,22]. Netosis has been documented in most species, including horses [23,24], and this active mechanism of cell death warrants further investigation in potential roles in pathogenesis, diagnosis and therapeutic targets for mild-moderate asthma with an associated bacterial component.…”