Immunity and Inflammation in the Uterus

Abstract

Contents Microbes often infect the uterus and particularly the endometrium of animals. Infections are most commonly associated with natural service, pregnancy and the post‐partum period, leading to inflammation with the elaboration of cytokines, chemokines and prostaglandins. Clinical diseases such as metritis, endometritis and abortion are important causes of infertility. The adaptive immune response to infection has been characterized previously, so the present review aims to highlight the emerging role for innate immunity in the endometrium. The detection of microbes and the innate immune response depends on the detection of pathogen‐associated molecular patterns by pattern recognition receptors. The main families of pattern recognition receptors are Toll‐like receptors (TLRs), nucleotide oligomerization domain‐like receptors, retinoic acid‐inducible gene I‐like receptors and C‐type lectin receptors. These receptors are most often expressed by hematopoietic cells, but the epithelial and stromal cells of the endometrium also possess functional receptors. For example, endometrial cells express TLR4 for recognition of the lipopolysaccharide endotoxin of Gram‐negative bacteria, leading to secretion of IL‐6, IL‐8 and prostaglandin E2. It is likely that the epithelial and stromal cells provide a first line of defence in the endometrium to alert hematopoietic cells to the presence of microbes within the uterus.

Relationship between TLR4 and MCP2 expression levels and habitual abortion

“…The birth of a new life is an extremely complex and regulated process, and involves the immunological interactions between maternal and paternal gametes, the maternal immunological function, expression of genes inherited from both parents, and chromosome structure (Wilding et al, 2004;Burrough et al, 2011;Turner et al, 2012;Xie et al, 2014). At present, habitual abortion not only seriously affects the patient's psychological and physiological health, but the quality of life of the patient's family.…”

Involvement of TLR7 and TLR8 in conceptus development and establishment of pregnancy in sheep

“…The increase in expression of TLR2, TLR7, TLR8, and TLR9 in the endometrium during early pregnancy probably results from both progesterone-dependent recruitment of immune cells enriched in these particular TLRs (Segerson et al 1991, Plaks et al 2008, Gomez-Lopez et al 2010, Mansouri-Attia et al 2012 and changes in uterine gene expression required for pregnancy (Young et al 2004, Jorgenson et al 2005, Aflatoonian et al 2007, Hirata et al 2007, Turner et al 2012. In view of the significant increase in steady-state levels of both TLR7 and TLR8 mRNAs in uteri of early pregnant ewes, we determined cell-specific expression of TLR7 and TLR8 proteins to be particularly abundant in uterine LE and sGE and expressed in a temporal and cell-specific manner that differed due to reproductive TLR and establishment of pregnancy in sheep status, which supports results obtained from previous studies (Jorgenson et al 2005, Aflatoonian et al 2007, Hirata et al 2007.…”

“…The finding of TLRs in non-typical immune cells such as the epithelia (Young et al 2004, Turner et al 2012 has implicated these receptors in many physiological events besides pathogen recognition (Li et al 2010). Available evidence indicates potential involvement of TLRs in mammalian reproduction, which requires an appropriate inflammatory balance among steroid hormones, cytokines, and prostaglandins to assure cyclical uterine remodeling for establishment and maintenance of pregnancy (King & Critchley 2010, Ott & Gifford 2010, Dorniak et al 2011.…”

Modelo experimental de endometrite em vacas inoculadas com Escherichia coli inativada por meio de infusão uterina

“…A regulação da resposta imunológica determina a importância do endométrio para a manutenção da fertilidade das vacas, verificando-se que processos inflamatórios exacerbados e/ou persistentes são prejudiciais (Turner et al, 2012;Martins et al, 2013). O estradiol e a progesterona atuam na regulação da imunidade uterina, porém seus mecanismos de ação ainda não foram esclarecidos.…”

“…Apesar de as bactérias que causam infecções uterinas em humanos e bovinos serem diferentes, as vacas apresentam amplo potencial como modelos in vivo para estudar as interações patógeno-hospedeiro e os mecanismos relacionados com o controle da imunidade uterina (Herath et al, 2006;Sheldon e Bromfield, 2011).  A maioria dos estudos que visam compreender os mecanismos de modulação da imunidade uterina em bovinos é realizada in vitro, porém a perda da arquitetura do tecido e a alteração das relações intercelulares ocorridas após a remoção dos componentes da matriz extracelular podem influenciar na função do epitélio e do estroma endometriais (Herath et al, 2006;Borges et al, 2012) (Martins et al, 2011;Turner et al, 2012). Ao desencadear a resposta inflamatória, a E. coli e outros microrganismos com potencial patogênico alteram a integridade do endométrio, interferindo nas conexões intercelulares e na permeabilidade seletiva das células epiteliais.…”