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

Abstract

The cytokine IL-17A has been shown to play critical roles in host defense against bacterial and fungal infections at different epithelial sites, but its role in the defense of the mammary gland (MG) has seldom been investigated, although infections of the MG constitute the main pathology afflicting dairy cows. In this study, we showed that IL-17A contributes to the defense of the MG against Escherichia coli infection by using a mouse mastitis model. After inoculation of the MG with a mastitis-causing E. coli strain, the bacterial load increased rapidly, triggering an intense influx of leukocytes into mammary tissue and increased concentrations of IL-6, IL-22, TNF-α, and IL-10. Neutrophils were the first cells that migrated intensely to the mammary tissue, in line with an early production of CXCL2. Depletion of neutrophils induced an increased mammary bacterial load. There was a significant increase of IL-17–containing CD4+ αβ T lymphocyte numbers in infected glands. Depletion of IL-17A correlated with an increased bacterial colonization and IL-10 production. Intramammary infusion of IL-17A at the onset of infection was associated with markedly decreased bacterial numbers, decreased IL-10 production, and increased neutrophil recruitment. Depletion of CD25+ regulatory T cells correlated with a decreased production of IL-10 and a reduced bacterial load. These results indicate that IL-17A is an important effector of MG immunity to E. coli and suggest that an early increased local production of IL-17A would improve the outcome of infection. These findings point to a new lead to the development of vaccines against mastitis.

Variation in fibroblast expression of toll-like receptor 4 and lipopolysaccharide-induced cytokine production between animals predicts control of bacterial growth but not severity of Escherichia coli mastitis

“…This result agrees with previous literature stating that antibody response is not a major contributor to E. coli or S. aureus clearance within the mammary gland (Benjamin et al, 2015;Herry et al, 2017). The role of the adaptive response in determining between-cow differences in mastitis severity and duration should be the subject of future research, specifically the role of Th-17 cells, which have been shown to be the predominant T-cell responder in E. coli mastitis (Porcherie et al, 2016) and are associated with a primarily neutrophilic response. However, other immune cell types whose functions remain unknown in bovine mastitis, such as innate lymphoid cells that are present in high numbers in mucosal tissue and γδ T cells that are expressed at much higher levels in the bovine than other species, may also contribute to differences in mastitis severity.…”

Mammary microbiota of dairy ruminants: fact or fiction?

“…Therefore, it could be possible to harness this microbiota or the tolerance to some microorganisms to enhance the resistance or resilience of the MG to mastitis-causing pathogens through the use of well-chosen probiotics. Although regulatory T cells have been found in the mouse mammary gland [81], published results to date do not support this possibility. Alternatively, if we posit that the normal MG is a sterile organ, then we can expect that any microorganism penetrating the lumen of the gland would trigger a response from the MG as soon as the threshold of reactivity was reached, because a sterile organ is not poised to tolerate a microbiota.…”

Local immunization impacts the response of dairy cows to Escherichia coli mastitis

“…Recently it has been shown with mouse mastitis models that IL-17A and Th17 cells are instrumental in the defense of the mammary gland against infection by E. coli or Staphylococcus aureus 7, 8 . It is also possible to induce an antigen-specific neutrophilic inflammation in the bovine mammary gland which correlates with the production of IL-17A and IFN-γ and with circulating Th17 cells and the presence of IL-17A in milk 9 .…”