Innate immune response of bovine mammary gland to pathogenic bacteria responsible for mastitis

2007 ◽  
Vol 54 (4) ◽  
pp. 399-409 ◽  
Author(s):  
Javier Oviedo-Boyso ◽  
Juan J. Valdez-Alarcón ◽  
Marcos Cajero-Juárez ◽  
Alejandra Ochoa-Zarzosa ◽  
Joel E. López-Meza ◽  
...  
2010 ◽  
Vol 77 (4) ◽  
pp. 404-410 ◽  
Author(s):  
Maria Mazzilli ◽  
Alfonso Zecconi

Non-specific (innate) immune response plays a major role in defending the udder from bacterial invasion. Moreover, recent investigations suggest that mammary gland epithelial cells (MGEC) could have a large and important role as a source of soluble components of immune defences. Despite many attempts to find other ways to control/prevent mastitis (i.e. vaccine) antimicrobial therapy is still the most used and effective means of curing clinical and subclinical mastitis. However, drug concentrations and therapy durations are far from the optimal in order to reduce costs. Therefore, efficacy of antimicrobial therapy is dependent not only on the substance activity but also on the positive interactions with the host innate immune response. Surprisingly, information on these interactions is rather scarce in the mastitis field. A simple experimental model was developed based on BME-UV cell line, Staphylococcus aureus as a challenge and a macrolide as an antimicrobial to assess the interactions among epithelial cells, Staph. aureus and the potential effects of antimicrobials on the immune system. The results of this study confirmed that tylosin has good antimicrobial activity against both intracellular and extracellular Staph. aureus in bovine MGEC without affecting cell functions. In this study, a significant down-regulation of IL-1 and IL-6 was observed, while TNF and IL-8 expression rate numerically increased, but differences were not significant. To our knowledge, this is the first paper assessing the concentration of two lysosomal enzymes, lysozyme and N-acetyl-β-d-glucosaminidase (NAGase), in Staph. aureus-stimulated MGEC. The results of this study confirmed that tylosin could have a significant effect on the release of these enzymes. Moreover, even if both enzymes have a similar substrate as a target, the results suggest different secretion mechanisms and an influence of antimicrobial treatment on these mechanisms. Successful mastitis cure is the result of achieving the optimal efficiency of both innate immune defences and therapeutical activities, by means of killing bacteria without eliciting an excessive inflammatory response. Therefore, antimicrobials for mastitis therapy should be selected not only on bacterial sensitivity, but also for their positive interactions with the innate immune response of the mammary gland. This study showed that an in-vitro model based on Staph. aureus challenge on MGEC could be helpful in assessing both the intracellular and extracellular activity of antimicrobials and their influence on epithelial cell immune and inflammatory response.


ExRNA ◽  
2019 ◽  
Vol 1 (1) ◽  
Author(s):  
Ava Behrouzi ◽  
Marjan Alimohammadi ◽  
Amir Hossein Nafari ◽  
Mohammad Hadi Yousefi ◽  
Farhad Riazi Rad ◽  
...  

Abstract MicroRNAs are non-coding RNAs, playing an important role in regulating many biological pathways, such as innate immune response against various infections. Different studies confirm that many miRNAs act as important regulators in developing a strategy for the survival of Mycobacterium tuberculosis in the host cell. On the other hand, an innate immune response is one of the important aspects of host defense against Mycobacterium. Considering the importance of miRNAs during tuberculosis infection, we focused on studies that performed on the role of various miRNAs related to pathogenic bacteria, M. tuberculosis in the host. Also, we have introduced important miRNAs that can be used as a biomarker for the detection of Mycobacterium.


2007 ◽  
Vol 75 (8) ◽  
pp. 3969-3978 ◽  
Author(s):  
Megan Gentry ◽  
Joanna Taormina ◽  
Richard B. Pyles ◽  
Linsey Yeager ◽  
Michelle Kirtley ◽  
...  

ABSTRACT Francisella tularensis, an intracellular pathogen, is highly virulent when inhaled. Alveolar epithelial type I (ATI) and type II (ATII) cells line the majority of the alveolar surface and respond to inhaled pathogenic bacteria via cytokine secretion. We hypothesized that these cells contribute to the lung innate immune response to F. tularensis. Results demonstrated that the live vaccine strain (LVS) contacted ATI and ATII cells by 2 h following intranasal inoculation of mice. In culture, primary human ATI or ATII cells, grown on transwell filters, were stimulated on the apical (AP) surface with virulent F. tularensis Schu 4 or LVS. Basolateral (BL) conditioned medium (CM), collected 6 and 24 h later, was added to the BL surfaces of transwell cultures of primary human pulmonary microvasculature endothelial cells (HPMEC) prior to the addition of polymorphonuclear leukocytes (PMNs) or dendritic cells (DCs) to the AP surface. HPMEC responded to S4- or LVS-stimulated ATII, but not ATI, CM as evidenced by PMN and DC migration. Analysis of the AP and BL ATII CM revealed that both F. tularensis strains induced various levels of a variety of cytokines via NF-κB activation. ATII cells pretreated with an NF-κB inhibitor prior to F. tularensis stimulation substantially decreased interleukin-8 secretion, which did not occur through Toll-like receptor 2, 2/6, 4, or 5 stimulation. These data indicate a crucial role for ATII cells in the innate immune response to F. tularensis.


mBio ◽  
2019 ◽  
Vol 10 (5) ◽  
Author(s):  
Alain P. Gobert ◽  
Yvonne L. Latour ◽  
Mohammad Asim ◽  
Jordan L. Finley ◽  
Thomas G. Verriere ◽  
...  

ABSTRACT The reverse transsulfuration pathway is the major route for the metabolism of sulfur-containing amino acids. The role of this metabolic pathway in macrophage response and function is unknown. We show that the enzyme cystathionine γ-lyase (CTH) is induced in macrophages infected with pathogenic bacteria through signaling involving phosphatidylinositol 3-kinase (PI3K)/MTOR and the transcription factor SP1. This results in the synthesis of cystathionine, which facilitates the survival of pathogens within myeloid cells. Our data demonstrate that the expression of CTH leads to defective macrophage activation by (i) dysregulation of polyamine metabolism by depletion of S-adenosylmethionine, resulting in immunosuppressive putrescine accumulation and inhibition of spermidine and spermine synthesis, and (ii) increased histone H3K9, H3K27, and H3K36 di/trimethylation, which is associated with gene expression silencing. Thus, CTH is a pivotal enzyme of the innate immune response that disrupts host defense. The induction of the reverse transsulfuration pathway by bacterial pathogens can be considered an unrecognized mechanism for immune escape. IMPORTANCE Macrophages are professional immune cells that ingest and kill microbes. In this study, we show that different pathogenic bacteria induce the expression of cystathionine γ-lyase (CTH) in macrophages. This enzyme is involved in a metabolic pathway called the reverse transsulfuration pathway, which leads to the production of numerous metabolites, including cystathionine. Phagocytized bacteria use cystathionine to better survive in macrophages. In addition, the induction of CTH results in dysregulation of the metabolism of polyamines, which in turn dampens the proinflammatory response of macrophages. In conclusion, pathogenic bacteria can evade the host immune response by inducing CTH in macrophages.


2013 ◽  
Vol 81 (9) ◽  
pp. 3182-3197 ◽  
Author(s):  
Maria Filippa Addis ◽  
Salvatore Pisanu ◽  
Gavino Marogna ◽  
Tiziana Cubeddu ◽  
Daniela Pagnozzi ◽  
...  

ABSTRACTInvestigating the innate immune response mediators released in milk has manifold implications, spanning from elucidation of the role played by mammary epithelial cells (MECs) in fighting microbial infections to the discovery of novel diagnostic markers for monitoring udder health in dairy animals. Here, we investigated the mammary gland response following a two-step experimental infection of lactating sheep with the mastitis-associated bacteriumStreptococcus uberis. The establishment of infection was confirmed both clinically and by molecular methods, including PCR and fluorescentin situhybridization of mammary tissues. Proteomic investigation of the milk fat globule (MFG), a complex vesicle released by lactating MECs, enabled detection of enrichment of several proteins involved in inflammation, chemotaxis of immune cells, and antimicrobial defense, including cathelicidins and calprotectin (S100A8/S100A9), in infected animals, suggesting the consistent involvement of MECs in the innate immune response to pathogens. The ability of MECs to produce and release antimicrobial and immune defense proteins was then demonstrated by immunohistochemistry and confocal immunomicroscopy of cathelicidin and the calprotectin subunit S100A9 on mammary tissues. The time course of their release in milk was also assessed by Western immunoblotting along the course of the experimental infection, revealing the rapid increase of these proteins in the MFG fraction in response to the presence of bacteria. Our results support an active role of MECs in the innate immune response of the mammary gland and provide new potential for the development of novel and more sensitive tools for monitoring mastitis in dairy animals.


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