T Helper 17-Associated Cytokines Are Produced during Antigen-Specific Inflammation in the Mammary Gland

Abstract

Infectious mastitis cuts down milk production profitability and is a major animal welfare problem. Bacteria-induced inflammation in the mammary gland (MG) is driven by innate immunity, but adaptive immunity can modulate the innate response. Several studies have shown that it is possible to elicit inflammation in the MG by sensitization to an antigen subsequently infused into the lumen of the gland. The objective of our study was to characterize the inflammation triggered in the MG of cows sensitized to ovalbumin, by identifying the cytokines and chemokines likely to play a part in the reaction. Among immunized cows, responders mobilized locally high numbers of leukocytes. An overexpression of the genes encoding IL-17a, IL-17F, IL-21, IL-22 and INF-γ was found in milk cell RNA extracts in the early phase of the inflammatory response. At the protein level, IL-17A was detected in milk as soon as the first sampling time (8 h post-challenge), and both IL-17A and IFN-γ concentrations peaked at 12 to 24 h post-challenge. In mammary tissue from challenged quarters, overexpression of the genes encoding IL-17A, IL-17F, IL-21, IL-22, IL-26 and IFN-γ was observed. Neutrophil-attracting chemokines (CXCL3 and CXCL8) were found in milk, and overexpressed transcripts of chemokines attracting lymphocytes and other mononuclear leukocytes (CXCL10, CCL2, CCL5, CCL20) were detected in mammary tissue. Expression of IL-17A, as revealed by immunohistochemistry, was located in epithelial cells, in leukocytes in the connective tissue and in association with the epithelium, and in migrated alveolar leukocytes of challenged quarters. Altogether, these results show that antigen-specific inflammation in the MG was characterized by the production of IL-17 and IFN-γ. The orientation of the inflammatory response induced by the antigen-specific response has the potential to strongly impact the outcome of bacterial infections of the MG.

IL-17A Is an Important Effector of the Immune Response of the Mammary Gland to Escherichia coli Infection

“…This study clearly suggests that increasing the capacity of the MG to mount an IL-17-type response would help the MG to get rid of infections by Gram-negative bacteria. Along with our studies showing that Th17-like cytokines are produced in the bovine MG in vaccinated animals in response to an Ag-specific inflammatory response and that Th17 cells could be associated with the influx of neutrophils into the milk compartment (59,60), these new data constitute a strong incentive to study the effect of vaccination against mastitis-causing bacteria with a view to generating Th17 lymphocytes. These results also reveal that IL-17A, a cytokine known to play a prominent role in mucosal immunity to many extracellular and some intracellular pathogens (24,26,61), is also involved in the defense of the MG, a nonmucosal organ lined by a secretory epithelium.…”

Interferon stimulated genes as peripheral diagnostic markers of early pregnancy in sheep: a critical assessment

“…In dairy herds, mastitis is another recurrent source of infection. Bacterial infection of the mammary gland is locally characterized by neutrophilic inflammation, resulting in production of a large amount of interleukins and cytokines, including ISG (Rainard et al, 2013). Besides this local reaction, inflammatory response to mastitis involves systemic consequences such as leucocyte activation (Jiang et al, 2008) and enhanced expression of antimicrobial and cytokine genes (Mitterhuemer et al, 2010).…”

Produção de interleucina-1beta e severidade da mastite pós-inoculação de Staphylococcus aureus na glândula mamária de bovinos e bubalinos

“…A imunidade inata, a mais importante nesse tecido, é representada pelas barreiras físicas, fatores solúveis e fatores celulares (RAINARD et al, 2013).…”

“…As citocinas envolvidas na fi siopatologia da glândula mamária são as interleucinas, interferon-γ e o fator de necrose tumoral-α (SORDILLO et al, 1997;RAINARD et al, 2013). A IL-1β, uma das citocinas pró-infl amatórias mais avaliadas, provoca uma resposta local pela migração transepitelial de neutrófi los, e uma resposta sistêmica, por ser uma potente indutora da febre (WATSON et al, 2011).…”