RESUMO
Chlamydia abortus is an obligate intracellular bacterium that is an important cause of ovine abortion worldwide. There are reports of abortions in cattle, but these are very rare compared to the reported incidence in sheep. The bacterium is transmitted oro-nasally and can establish a sub-clinical infection until pregnancy, when it can invade the placenta and induce an inflammatory cascade leading to placentitis and abortion. Early host-pathogen interactions could explain differential pathogenesis and subsequent disease outcome in ruminant species. In this study, we assessed the ability of sheep and cattle oro-nasal turbinate cells to sense and respond to C. abortus infection. The cells expressed toll like receptor (TLR) 2, TLR4, nucleotide oligomerization domain (NOD) 1 and NOD-like receptor pyrin domain containing 3 (NLRP3) mRNA. In response to C. abortus infection, both ovine and bovine turbinate cells produce CXCL8 mRNA and protein late in the bacterial developmental cycle, but do not produce IL-1ß or TNF-α. The UV-inactivated bacteria did not elicit a CXCL8 response, suggesting that intracellular multiplication of the bacteria is important for activating the signalling pathways. The production of innate immune cytokines from cattle and sheep turbinate cells in response to C. abortus infection was found to be largely similar.
Assuntos
Aborto Animal/imunologia , Doenças dos Bovinos/imunologia , Infecções por Chlamydia/veterinária , Interleucina-8/biossíntese , Ovinos/imunologia , Aborto Animal/genética , Animais , Bovinos , Células Cultivadas , Infecções por Chlamydia/genética , Infecções por Chlamydia/imunologia , Citocinas/biossíntese , Citocinas/genética , Feminino , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Imunidade Inata , Interleucina-8/genética , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Reconhecimento de Padrão/biossíntese , Receptores de Reconhecimento de Padrão/genética , Doenças dos Ovinos , Carneiro Doméstico , Especificidade da Espécie , Conchas Nasais/citologia , Conchas Nasais/imunologiaRESUMO
Indirect tests of bronchial responsiveness to agents such as adenosine 5'-monophosphate (AMP) or bradykinin might be more specific markers of a therapeutic responses to anti-inflammatory treatment than a test of direct responsiveness to agents such as methacholine. In children selected from the community on the basis of mildly symptomatic wheeze, we compared in a randomized, double-blind study design the effect of 400 micrograms/day of beclomethasone dipropionate (BDP) or placebo on three separate ways of provoking bronchial responsiveness, using methacholine, bradykinin, and AMP as the provoking agents. Following pretreatment bronchial challenges, 29 children received paired monthly methacholine and AMP challenges for 3 months, while for the same period another 33 children received paired monthly methacholine and bradykinin challenges. Compared with placebo-treated subjects, FEV1 increased significantly in the children receiving BDP. This improvement was observed in those randomized to either the AMP challenge or the bradykinin challenge. In children challenged with AMP, the PD20 AMP increased significantly after 1 month and 2 months of BDP therapy when compared with placebo, while under similar conditions the PD20 methacholine was not significantly affected. In children challenged with bradykinin, BDP therapy did not significantly alter either the PD20 bradykinin or PD20 methacholine. We conclude that a bronchial challenge with AMP appears to be a more sensitive predictor of response to anti-inflammatory treatment than either methacholine or bradykinin.
