Mucosal immunity of the postpartum bovine genital tract
Introduction
The bovine female genital tubular system is functionally adapted to facilitate oocyte fertilization, nurture embryonic/fetal development, deliver a calf, and ensure a timely return to a pre-gravid state. Immunologically, the female genital system exhibits a large degree of flexibility from what is believed to be an immunotolerant state during pregnancy to the ability to mount active immune responses when encountering genital pathogens. The mechanisms of immunosuppression during bovine pregnancy have been extensively reviewed [1], [2], [3] and will not be covered in the present report. The current review will focus on knowledge of innate and acquired mucosal immune responses and their regulation during the postpartum period (up to 60 days in milk) in cattle.
The female genital tubular tract has several known physical barriers to minimize bacterial entry and colonization. These include vulvar sealing, vestibule-vaginal constriction, the cervix, cervico-vaginal mucus secretion, and the epithelial barrier, but until recently an in depth understanding of these and other protective mechanisms at a cellular and molecular level was lacking. Classically, mucosal sites such as the intestine, respiratory tract, and ocular mucosa are associated with organized sub-mucosal lymphoid tissue, collectively referred to as mucosal-associated lymphoid tissues (MALT), that is populated by both T- and B-lymphocytes [4]. The MALT constitutes a crucial inductive site for both antibody-dependent humoral (mainly immunoglobulin (Ig) A) and cellular immune responses against potential antigens. Isolated lymphoid aggregates (follicles) and isolated lymphoid infiltrations have been observed in the vestibule and throughout the rest of female genital tract of cattle, respectively [5]. Lymph fluid from the bovine uterus drains primarily to the internal iliac and sacral lymph nodes, which also function as important immune induction sites [6].
The following sections will focus on mucosal defense mechanisms of the bovine tubular genital tract during the postpartum period. Integration of epithelial cell function and immune mechanisms is crucial for maintaining the integrity of the mucosal barrier and this interaction will be emphasized. Where necessary, information from other species is incorporated to provide a comparative analysis of immune function and to highlight knowledge deficits that need to be addressed to better understand the function of the bovine postpartum uterus.
Section snippets
Genital tract inflammation during the postpartum period
Following delivery of a calf, the bovine genital tract undergoes an active inflammatory process to clear cellular debris from the placenta and respond to bacterial contamination. In healthy cows, uterine inflammation subsides by the fourth to fifth wk postpartum, however, genital tract (mainly uterus) reparation is not complete until the sixth to eighth wk postpartum [7]. Some cows will, however, exhibit either a systemic inflammatory response during the first two wk postpartum or will
Epithelial cells
The mucosal epithelial lining of the genital tract offers a physical defense mechanism against microbial attachment and invasion. The type of mucosal epithelium and the thickness of this layer varies with the anatomical location, responding to differing physiological needs (Fig. 1). A multilayered squamous epithelium in the vestibule and vagina [5] is important as these sites are the first to be challenged by bacteria from fecal, uterine and environmental origins. Extensive folding of the
Microflora
Bacterial contamination of the uterus from vaginal, fecal and environmental microflora occurs for two to three wk postpartum due to calving-associated relaxation of physical barriers, including an open cervix. Negative pressure events created by repeated uterine contraction and relaxation during this period enhances bacterial contamination by virtue of a vacuum effect. Regardless of circumstances, Gram-negative bacteria predominate in all bovine uteri during the first wk after calving and are
Conclusions
The bovine genital tract, like other mucosal surfaces, has an epithelium that can respond to PAMPs and DAMPs, eliciting local activation and recruitment of innate immune cells. Substantial knowledge has been acquired regarding the innate and acquired immune defense mechanisms present throughout the bovine genital tract (Table 1). For example, while the genital tract does not have specialized mucosa-associated lymphoid tissues, as seen in the gastro-intestinal and respiratory tracts, isolated
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