Natural defenses: Different responses for different bacteria

The outcome of any infectious threat is determined by both host and pathogen factors. The immunological responses to infection by E.coli or S. aureus are compared to show how the host (cow) response differs. These response differences may explain the differences in mastitis infections caused by these 2 organisms

Introduction

Establishment and persistence of infection is mediated by both intrinsic properties of the pathogen itself (22) and the nature of the host’s response to the pathogen (15). The immune system, comprised of both innate and acquired components, is responsible for responding to and protecting against infection. The innate immune systems is the first line of active defense against invading pathogens once they have penetrated the physical barriers of the skin and other tissues, such as the streak canal of the teat (57). The innate system is poised to respond immediately to the earliest stages of infection and to recognize pathogens that have not been previously encountered.

This contrasts with the acquired (adaptive) immune response, which requires several days to generate effector cells (i.e., lymphocytes) at levels necessary to exert protective responses to infection. The outcome of intramammary infection, either host eradication of the pathogen or the establishment of persistent chronic infection, is often governed by events in the immediate hours and days following initial infection (25, 27, 28).

Thus, the innate branch of the immune system, which elicits the immediate responses to infection, is the primary host determinant of the outcome of intramammary infection.

Innate Immune Recognition of Pathogens

The majority of cases of mastitis are caused by bacterial intramammary infections. A numerous and diverse spectrum of bacteria can be involved.

The ability of the innate immune system to respond to this vast array of pathogens, even at first exposure, is mediated by its ability to recognize highly conserved motifs expressed by these pathogens. These motifs are commonly referred to as pathogen-associated molecular patterns (PAMP’S) and include the bacterial cell membrane and wall components.

S. aureus and E. coli Intramammary Infection

S. aureus and E. coli are among the most prevalent Gram-positive and Gram-negative bacteria, respectively, to cause intramammary infections in dairy cattle (13). Striking differences exist in the clinical course and outcome of mastitis caused by these two pathogens. Intramammary infection by E. coli is acute in nature and in mid- to late-lactating cows these infections generally clear within a few days (47). S. aureus causes intramammary infections that are often subclinical and often establishes chronic infections that can persist for the life of the animal (53). Difference in the severity and outcome of mastitis that accompany intramammary infection by E. coli and S. aureus may be attributed to the differential host immune responses that each organism elicits.

Distinct Innate Immune Responses to S. aureus

The innate immune response elicited by intramammary infection with E. coli was compared to that caused by S. aureus (12). Intramammary infection with either organism evoked a systemic response that included decreased milk output, increased core body temperature, and induction of acute phase protein synthesis. The febrile response was more acute and heightened in E. coli infected cows than those infected with S. aureus. Acute phase bacterial protein synthesis was comparable in terms of magnitude and duration between cows infected with either organism, although the onset was more rapid in those infected with E. coli. Quarters infected with E.coli or S. aureus showed localized signs of inflammation including increased permeability of the mammary vasculature and elevated levels of milk SCC. Similar to acute phase bacterial protein synthesis, the peak magnitude of these responses were comparable, but the onset was delayed in S. aureus-infected quarters. Further, the duration of increased mammary vascular permeability was more abbreviated in S. aureus-infected quarters than in those infected with E.coli. Another component of the innate immune response, complement activation, was also evident in both S. aureus and E. coli infected glands, although the peak magnitude and duration were less in quarters with S. aureus.

The most striking differences in the innate immune responses were in the production of specific cytokines. Whereas three specific pro-inflammatory cytokines were induced in response to E. coli, there was virtually no indication of any of these in S. aureus-infected quarters. Studies with several other mastitis pathogens, including both Gram-negative and Gram-positive bacteria, have all reported the induction of these cytokines during intramammary infection (8-10, 12-42). The surprising finding of a complete lack of induction of certain cytokines in S. aureus, appears to be generalizable to S. aureus and not due to strain variation.

Because the ability of bacteria to establish infection is determined, in part, by the ability of the host to respond to the invading organism (15), the lack of induction of the pro-inflammatory cytokines, may contribute to the ability of S. aureus to establish a chronic infection in the bovine mammary gland. This is clearly the case in other species, as pro-inflammatory cytokine-knockout mice have been used to demonstrate impaired clearance of S. aureus relative to wild-mice (23-50).

Further, recombinant cytokine therapy, has been shown to enhance S. aureus intramammary clearance in both cows and mice, respectively (45-54). Together, these data suggest that differences in the host immune response influence resolution of infection. Interventions which alter this response may have potential therapeutic benefit for the treatment of intramammary infections in cattle.

References

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Author

Douglas Bannerman

Douglas Bannerman
1 articles

Microbiologist - Bovine Functional Genomics Lab

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