The Role of Airway Epithelial Cells in Response to Mycobacteria Infection

Airway epithelial cells (AECs) are part of the frontline defense against infection of pathogens by providing both a physical barrier and immunological function. The role of AECs in the innate and adaptive immune responses, through the production of antimicrobial molecules and proinflammatory factors against a variety of pathogens, has been well established. Tuberculosis (TB), a contagious disease primarily affecting the lungs, is caused by the infection of various strains of mycobacteria. In response to mycobacteria infection, epithelial expression of Toll-like receptors and surfactant proteins plays the most prominent roles in the recognition and binding of the pathogen, as well as the initiation of the immune response. Moreover, the antimicrobial substances, proinflammatory factors secreted by AECs, composed a major part of the innate immune response and mediation of adaptive immunity against the pathogen. Thus, a better understanding of the role and mechanism of AECs in response to mycobacteria will provide insight into the relationship of epithelial cells and lung immunocytes against TB, which may facilitate our understanding of the pathogenesis and immunological mechanism of pulmonary tuberculosis disease

Isolation of Mycobacterium tuberculosis complex (MTBC) from dairy cows in China

Eleven thousand five hundred and eighty non-blood samples from dairy cows were subjected to mycobacterium culture and genotyping. As a result, a total of 142 isolates of Mycobacterium tuberculosis complex (MBTC) were identified. Among them, 65 were Mycobacterium tuberculosis, while 77 Mycobacterium bovis. The genotype of M. tuberculosis strains was mainly Beijing family. In addition, the isolation rates of MTBC were 33.89% for lung lymph nodes, 2.81% for nasal swabs, and 3.95% for pharyngeal swabs from cattle positive to tuberculin skin test, respectively. This evidence implied that M. tuberculosis infection in cattle is a new risk to public health and should be paid more attention.Key words: Mycobacterium tuberculosis complex, cows, tuberculosis, zoonosis

Comparative proteome analysis revealed the differences in response to both Mycobacterium tuberculosis and Mycobacterium bovis infection of bovine alveolar macrophages

Tuberculosis (TB), attributed to the Mycobacterium tuberculosis complex, is one of the most serious zoonotic diseases worldwide. Nevertheless, the host mechanisms preferentially leveraged by Mycobacterium remain unclear. After infection, both Mycobacterium tuberculosis (MTB) and Mycobacterium bovis (MB) bacteria exhibit intimate interactions with host alveolar macrophages; however, the specific mechanisms underlying these macrophage responses remain ambiguous. In our study, we performed a comparative proteomic analysis of bovine alveolar macrophages (BAMs) infected with MTB or MB to elucidate the differential responses of BAMs to each pathogen at the protein level. Our findings revealed heightened TB infection susceptibility of BAMs that had been previously infected with MTB or MB. Moreover, we observed that both types of mycobacteria triggered significant changes in BAM energy metabolism. A variety of proteins and signalling pathways associated with autophagy and inflammation-related progression were highly activated in BAMs following MB infection. Additionally, proteins linked to energy metabolism were highly expressed in BAMs following MTB infection. In summary, we propose that BAMs may resist MTB and MB infections via different mechanisms. Our findings provide critical insights into TB pathogenesis, unveiling potential biomarkers to facilitate more effective TB treatment strategies. Additionally, our data lend support to the hypothesis that MTB may be transmitted via cross-species infection

Capsular Polysaccharide of Mycoplasma ovipneumoniae

In an attempt to better understand the pathogen-host interaction between invading Mycoplasma ovipneumoniae (M. ovipneumoniae) and sheep airway epithelial cells, biological effects and possible molecular mechanism of capsular polysaccharide of M. ovipneumoniae (CPS) in the induction of cell apoptosis were explored using sheep bronchial epithelial cells cultured in air-liquid interface (ALI). The CPS of M. ovipneumoniae was first isolated and purified. Results showed that CPS had a cytotoxic effect by disrupting the integrity of mitochondrial membrane, accompanied with an increase of reactive oxygen species and decrease of mitochondrial membrane potential (ΔΨm). Of importance, the CPS exhibited an ability to induce caspase-dependent cell apoptosis via both intrinsic and extrinsic apoptotic pathways. Mechanistically, the CPS induced extrinsic cell apoptosis by upregulating FAS/FASL signaling proteins and cleaved-caspase-8 and promoted a ROS-dependent intrinsic cell apoptosis by activating a JNK and p38 signaling but not ERK1/2 signaling of mitogen-activated protein kinases (MAPK) pathways. These findings provide the first evidence that CPS of M. ovipneumoniae induces a caspase-dependent apoptosis via both intrinsic and extrinsic apoptotic pathways in sheep bronchial epithelial cells, which may be mainly attributed by a ROS-dependent JNK and p38 MAPK signaling pathways

Gene editing tools for mycoplasmas: references and future directions for efficient genome manipulation

Mycoplasmas are successful pathogens that cause debilitating diseases in humans and various animal hosts. Despite the exceptionally streamlined genomes, mycoplasmas have evolved specific mechanisms to access essential nutrients from host cells. The paucity of genetic tools to manipulate mycoplasma genomes has impeded studies of the virulence factors of pathogenic species and mechanisms to access nutrients. This review summarizes several strategies for editing of mycoplasma genomes, including homologous recombination, transposons, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system, and synthetic biology. In addition, the mechanisms and features of different tools are discussed to provide references and future directions for efficient manipulation of mycoplasma genomes

X (2012) The role of airway epithelial cells in response to mycobacteria infection. Clin Dev Immunol 2012: 791392

Airway epithelial cells (AECs) are part of the frontline defense against infection of pathogens by providing both a physical barrier and immunological function. The role of AECs in the innate and adaptive immune responses, through the production of antimicrobial molecules and proinflammatory factors against a variety of pathogens, has been well established. Tuberculosis (TB), a contagious disease primarily affecting the lungs, is caused by the infection of various strains of mycobacteria. In response to mycobacteria infection, epithelial expression of Toll-like receptors and surfactant proteins plays the most prominent roles in the recognition and binding of the pathogen, as well as the initiation of the immune response. Moreover, the antimicrobial substances, proinflammatory factors secreted by AECs, composed a major part of the innate immune response and mediation of adaptive immunity against the pathogen. Thus, a better understanding of the role and mechanism of AECs in response to mycobacteria will provide insight into the relationship of epithelial cells and lung immunocytes against TB, which may facilitate our understanding of the pathogenesis and immunological mechanism of pulmonary tuberculosis disease

A Survey on Service Migration in Mobile Edge Computing

Mobile edge computing (MEC) provides a promising approach to significantly reduce network operational cost and improve quality of service (QoS) of mobile users by pushing computation resources to the network edges, and enables a scalable Internet of Things (IoT) architecture for time-sensitive applications (e-healthcare, real-time monitoring, and so on.). However, the mobility of mobile users and the limited coverage of edge servers can result in significant network performance degradation, dramatic drop in QoS, and even interruption of ongoing edge services; therefore, it is difficult to ensure service continuity. Service migration has great potential to address the issues, which decides when or where these services are migrated following user mobility and the changes of demand. In this paper, two conceptions similar to service migration, i.e., live migration for data centers and handover in cellular networks, are first discussed. Next, the cutting-edge research efforts on service migration in MEC are reviewed, and a devisal of taxonomy based on various research directions for efficient service migration is presented. Subsequently, a summary of three technologies for hosting services on edge servers, i.e., virtual machine, container, and agent, is provided. At last, open research challenges in service migration are identified and discussed.Mobile edge computing (MEC) provides a promising approach to significantly reduce network operational cost and improve quality of service (QoS) of mobile users by pushing computation resources to the network edges, and enables a scalable Internet of Things (IoT) architecture for time-sensitive applications (e-healthcare, real-time monitoring, and so on.). However, the mobility of mobile users and the limited coverage of edge servers can result in significant network performance degradation, dramatic drop in QoS, and even interruption of ongoing edge services; therefore, it is difficult to ensure service continuity. Service migration has great potential to address the issues, which decides when or where these services are migrated following user mobility and the changes of demand. In this paper, two conceptions similar to service migration, i.e., live migration for data centers and handover in cellular networks, are first discussed. Next, the cutting-edge research efforts on service migration in MEC are reviewed, and a devisal of taxonomy based on various research directions for efficient service migration is presented. Subsequently, a summary of three technologies for hosting services on edge servers, i.e., virtual machine, container, and agent, is provided. At last, open research challenges in service migration are identified and discussed.This work was supported by NSFC under Grant 61472047This work was supported by NSFC under Grant 6147204

Epidemiological investigation of non-albicans Candida species recovered from mycotic mastitis of cows in Yinchuan, Ningxia of China

Abstract Background Candida spp. is the vital pathogen involved in mycotic mastitis of cows. However the epidemiology and infection of Candida species in mycotic mastitis of cow in Ningxia province of China has not been explored. In the present study, the epidemiology, antimicrobial susceptibility and virulence-related genes of non-albicans Candida (NAC) species were investigated. Methods A total of 482 milk samples from cows with clinical mastitis in four herds of Yinchuan, Ningxia were collected and used for the isolation and identification of mastic pathogens by phenotypic and molecular characteristics, and matrix-assisted laser desorption ionization-time of flight mass spectrometry. The antimicrobial susceptibility to antifungal agents was also determined by a disk diffusion assay. The presence of virulence-related genes was determined by polymerase chain reaction (PCR). Results A total of 60 isolates from nine different Candida species were identified from 256 (60/256, 23.44%) milk samples. The most frequently identified species in cows with clinical mastitis groups were Candida krusei (n = 14) and Candida parapsilosis (n = 6). Others include Candida lipolytica, Candida lusitaniae, Cryptococcus neoformans. But no Candida albicans was identified in this study. Interestingly, All C. krusei isolates (14/14) were resistant to fluconazole, fluorocytosine, itraconazole and ketoconazole, 2 out of 14 C. krusei were resistant to amphotericin, and 8 out of the 14 were resistant to nystatin. Similarly, all six C. parapsilosis isolates were resistant to fluorocytosine, but susceptible to fluconazole, ketoconazole and nystatin; two of the six were resistant amphotericin and itraconazole. Molecularly, all of the C. parapsilosis isolates carried eight virulence-related genes, FKS1, FKS2, FKS3, SAP1, SAP2, CDR1, ERG11 and MDR1. All of the C. krusei isolates contained three virulence-related genes, ERG11, ABC2 and FKS1. Conclusion These data suggested that Candida species other than C. albicans played a pathogenic role in mycotic mastitis of cows in Yinchuan, Ningxia of China. The high incidence of drug-resistant genes in C. parapsilosis and C. krusei also highlighted a great concern in public and animal health in this region

Effects of Total Alkaloids of Sophora alopecuroides on Biofilm Formation in Staphylococcus epidermidis

Staphylococcus epidermidis (S. epidermidis) is an opportunistic pathogen with low pathogenicity and a cause of the repeated outbreak of bovine mastitis in veterinary clinical settings. In this report, a biofilm model of S. epidermidis was generated and the minimal inhibitory concentration (MIC) and sub-MIC (SMIC) on bacterial cultures were assessed for the following agents: total alkaloids of Sophora alopecuroides (TASA), ciprofloxacin (CIP), and erythromycin (ERY). The formation and characteristic parameters of biofilm were analyzed in terms of XTT assay, silver staining, and confocal laser scanning microscope (CLSM). Results showed that a sub-MIC of TASA could inhibit 50% biofilm of bacterial activity, while 250-fold MIC of CIP and ERY MICs only inhibited 50% and 47% of biofilm formation, respectively. All three agents could inhibit the biofilm formation at an early stage, but TASA showed a better inhibitory effect on the late stage of biofilm thickening. A morphological analysis using CLSM further confirmed the destruction of biofilm by these agents. These results thus suggest that TASA has an inhibitory effect on biofilm formation of clinic S. epidermidis, which may be a potential agent warranted for further study on the treatment prevention of infection related to S. epidermidis in veterinary clinic