Th17-related mammary immunity, but not a high systemic Th1 immune response is associated with protection against E. coli mastitis

Cebron, Nathan; Maman, Sarah; Walachowski, Sarah; Gausserès, Blandine; Cunha, Patricia; Rainard, Pascal; Foucras, Gilles

doi:10.1038/s41541-020-00258-4

Cited by 17 publications

(12 citation statements)

References 39 publications

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“…Experiments with immunized mice are awaited to unravel the role of T cell immunity in the anamnestic response of the MG to infections. The relevance of the mouse mastitis model is supported by the observation that local immunization of the MG of cows during the dry period after priming by the intramuscular route elicited resident Th17 cells in the mammary tissue and an increased production of IL-17 in the tissue compared to unimmunized control glands upon infection challenge with E. coli ( 117 ). This immune response was associated with an improved control of infection ( 118 ).…”

Section: The Mammary Gland As An Immune Effector Site Of Adaptive Cel...mentioning

confidence: 99%

Adaptive Cell-Mediated Immunity in the Mammary Gland of Dairy Ruminants

2022

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Mastitis is one of the greatest issues for the global dairy industry and controlling these infections by vaccination is a long-sought ambition that has remained unfulfilled so far. In fact, gaps in knowledge of cell-mediated immunity in the mammary gland (MG) have hampered progress in the rational design of immunization strategies targeting this organ, as current mastitis vaccines are unable to elicit a strong protective immunity. The objectives of this article are, from a comprehensive and critical review of available literature, to identify what characterizes adaptive immunity in the MG of ruminants, and to derive from this analysis research directions for the design of an optimal vaccination strategy. A peculiarity of the MG of ruminants is that it does not belong to the common mucosal immune system that links the gut immune system to the MG of rodents, swine or humans. Indeed, the MG of ruminants is not seeded by lymphocytes educated in mucosal epithelia of the digestive or respiratory tracts, because the mammary tissue does not express the vascular addressins and chemokines that would allow the homing of memory T cells. However, it is possible to elicit an adaptive immune response in the MG of ruminants by local immunization because the mammary tissue is provided with antigen-presenting cells and is linked to systemic mechanisms. The optimal immune response is obtained by luminal exposure to antigens in a non-lactating MG. The mammary gland can be sensitized to antigens so that a local recall elicits neutrophilic inflammation and enhanced defenses locally, resulting from the activation of resident memory lymphocytes producing IFN-γ and/or IL-17 in the mammary tissue. The rational exploitation of this immunity by vaccination will need a better understanding of MG cell-mediated immunity. The phenotypic and functional characterization of mammary antigen-presenting cells and memory T cells are amongst research priorities. Based on current knowledge, rekindling research on the immune cells that populate the healthy, infected, or immunized MG appears to be a most promising approach to designing efficacious mastitis vaccines.

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Section: The Mammary Gland As An Immune Effector Site Of Adaptive Cel...mentioning

confidence: 99%

Adaptive Cell-Mediated Immunity in the Mammary Gland of Dairy Ruminants

2022

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“…Moreover, the humoral response is not the only immune response that could be induced by Omps and that could be beneficial to the host. Cell-mediated immune responses, a neglected area of research in the mastitis field until recently, may prove to be a promising lead to the development of new vaccines (44). In this view, antibody titers may not be a good correlate of protection, particularly those antibodies that bind to rough E. coli strains.…”

Section: Figmentioning

confidence: 99%

Shielding Effect of Escherichia coli O-Antigen Polysaccharide on J5-Induced Cross-Reactive Antibodies

Rainard

Répérant-Ferter

Gitton

et al. 2021

mSphere

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Escherichia coli is the leading cause of severe mastitis in dairy farms. As E. coli mastitis is refractory to the hygienic control measures adapted to contagious mastitis, efficient vaccines are in demand. Existing mastitis vaccines, based on the use of killed rough E. coli J5 as the antigen, aim at inducing phagocytosis by neutrophils. We assessed the binding of J5-induced antibodies to isogenic rough and smooth strains along with a panel of mastitis-associated E. coli. Analysis by enzyme-linked immunosorbent assay revealed that antibodies to OmpA or killed J5 bind readily to rough E. coli but poorly to smooth strains. Flow cytometry analysis indicated that immunization with J5 induced antibodies that cross-reacted with rough E. coli strains but with only a small subpopulation of smooth strains. We identified type 1 fimbriae as the target of most antibodies cross-reacting with the smooth strains. These results suggest that the O-polysaccharide of lipopolysaccharide shields the outer membrane antigens and that only fiber antigens protruding at the bacterial surface can elicit antibodies reacting with mastitis-associated E. coli. We evaluated J5-induced antibodies in an opsonophagocytic killing assay with bovine neutrophils. J5 immune serum was not more efficient than preimmune serum, showing that immunization did not improve on the already high efficiency of naturally acquired antibodies to E. coli. In conclusion, it is unlikely that the efficiency of J5 vaccines is related to the induction of opsonic antibodies. Consequently, other research directions, such as cell-mediated immunity, should be explored to improve E. coli mastitis vaccines. IMPORTANCE Despite intensive research, mastitis remains an important disease in dairy cattle with a significant impact on animal welfare, use of antibiotics, and, in the end, the economy of dairy farms. Although vaccines available so far have shown limited efficacy against coliform mastitis, vaccination is considered one of the measures that could limit the consequences of mastitis. One reason for the lack of efficiency of current vaccines likely stems from the current evaluation of vaccines that relies mostly on measuring antibody production against vaccine antigens. This report clearly shows that vaccine-induced antibodies fail to bind to most mastitis-associated E. coli strains because of the presence of an O-antigen and, thus, do not allow for improved phagocytosis of pathogens. As a consequence, this report calls for revised criteria for the evaluation of vaccines and suggests that cell-mediated immunity should be targeted by new vaccinal strategies. More generally, these results could be extended to other vaccine development strategies targeting coliform bacteria.

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“…Based on our current understanding of the immunological responses in the mammary gland of ewes against bacterial mastitis, as discussed above. The significant role played by antibody-mediated immune response, such as the importance of induction of locally produced antigen-specific IgA antibodies [131], and cell-mediated immune response geared towards a local Th17 response at DOI: http://dx.doi.org/10.5772/intechopen.97585 the onset of infection in preventing mastitis [87,88,132], supports the use of novel vaccines technologies in the improvement of already existing experimental vaccine. For example, already licensed vaccines for bacterial mastitis used in sheep and goats, could be improved in the following manner:…”

Section: Approach To New Vaccine Developments For the Prevention Of Mastitismentioning

confidence: 99%

“…2. Use of delivery systems (formulation strategies and novel adjuvants) in order to stimulate the development of immunity towards a Th17 type response [132,134] and stimulate local production of IgA and IgG2 responses [135].…”

Section: Approach To New Vaccine Developments For the Prevention Of Mastitismentioning

confidence: 99%

“…3. Exploring alternative vaccination routes, such as mucosal vaccine administration, in order to achieve the desired immune response, for example, in cow vaccination route have an impact on the subsequent immune response [132,140,141]. For example, studies, have shown that intramammary administration of antigens (e.g., inactivated S. aureus) in non-lactating ewe enhance the kinetics of neutrophil influx with no involvement of complement in the immunological response.…”

Section: Approach To New Vaccine Developments For the Prevention Of Mastitismentioning

confidence: 99%

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Mastitis in Small Ruminants

Kahinda¹

2022

Mastitis in Dairy Cattle, Sheep and Goats

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Bacterial mastitis in small ruminants is a complex disease, with massive economic loss in dairy sheep/goat industry due to poor productivity. The current mastitis prevention strategy relies on culling of infected ewes or does and or the use of antimicrobial agents to eliminate the bacterial infection. This has a potential risk for developing antibiotic resistant bacteria, posing human health risk from consumption of raw sheep or goat dairy products. Existing experimental and licensed vaccines on the market are ineffective against reducing the risk of mastitis in herds or flocks. Raising the needs for development of improved vaccines against mastitis for use in sheep and goats. This review examines, current understanding of the pathological processes and immunological responses against bacterial mastitis, using S. aureus as an example. By highlighting the protective defense mechanism induced in the udder against S. aureus mastitis. Based on evidence from published studies on pathological process and protective immune response mechanism, the need for improved vaccines for prevention of mastitis in small ruminant is highlighted and the development of a vaccine capable of enhancing immune response mechanism, that reduce the establishment of intramammary infection through induction of local IgA, IgG2 and Th17 immune responses is proposed.

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Th17-related mammary immunity, but not a high systemic Th1 immune response is associated with protection against E. coli mastitis

Cited by 17 publications

References 39 publications

Adaptive Cell-Mediated Immunity in the Mammary Gland of Dairy Ruminants

Adaptive Cell-Mediated Immunity in the Mammary Gland of Dairy Ruminants

Shielding Effect of Escherichia coli O-Antigen Polysaccharide on J5-Induced Cross-Reactive Antibodies

Mastitis in Small Ruminants

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