scholarly journals Mycobacterial infection of precision cut lung slices reveals that the type 1 interferon pathway is locally induced by Mycobacterium bovis but not M. tuberculosis in different cattle breeds

2021 ◽  
Author(s):  
Aude Remot ◽  
Florence Carreras ◽  
Anthony Coupe ◽  
Emilie Doz-Deblauwe ◽  
Maria-Laura Boschiroli ◽  
...  
Keyword(s):  
Mycobacterium Bovis ◽  
Animal Health ◽  
Mycobacterial Infection ◽  
Developed Countries ◽  
Host Cells ◽  
Economic Losses ◽  
Reference Laboratory ◽  
Type I ◽  
Cattle Breeds ◽  
Interferon Pathway

Tuberculosis exacts a terrible toll on human and animal health. While Mycobacterium tuberculosis (Mtb) is restricted to humans, Mycobacterium bovis (Mb) is present in a large range of mammalian hosts. In cattle, bovine TB (bTB) is a notifiable disease responsible for important economic losses in developed countries and underestimated zoonosis in the developing world. Early interactions that take place between mycobacteria and the lung tissue early after aerosol infection govern the outcome of the disease. In cattle, these early steps remain poorly characterized. The precision-cut lung slice (PCLS) model preserves the structure and cell diversity of the lung. We developed this model in cattle in order to study the early lung response to mycobacterial infection. In situ imaging of PCLS infected with fluorescent Mb revealed bacilli in the alveolar compartment, adjacent or inside alveolar macrophages (AMPs) and in close contact with pneumocytes. We analyzed the global transcriptional lung inflammation signature following infection of PCLS with Mb and Mtb in two French beef breeds: Blonde d'Aquitaine and Charolaise. Whereas lungs from the Blonde d'Aquitaine produced high levels of mediators of neutrophil and monocyte recruitment in response to infection, such signatures were not observed in the Charolaise in our study. In the Blonde d'Aquitaine lung, whereas the inflammatory response was highly induced by two Mb strains, AF2122 isolated from cattle in the UK and Mb3601 circulating in France, the response against two Mtb strains, H37Rv the reference laboratory strain and BTB1558 isolated from zebu in Ethiopia, was very low. Strikingly, the type I interferon pathway was only induced by Mb but not Mtb strains indicating that this pathway may be involved in mycobacterial virulence and host tropism. Hence, the PCLS model in cattle is a valuable tool to deepen our understanding of early interactions between lung host cells and mycobacteria. It revealed striking differences between cattle breeds and mycobacterial strains. This model could help deciphering biomarkers of resistance versus susceptibility to bTB in cattle as such information is still critically needed for bovine genetic selection programs and would greatly help the global effort to eradicate bTB.

scholarly journals Mycobacterial Infection of Precision-Cut Lung Slices Reveals Type 1 Interferon Pathway Is Locally Induced by Mycobacterium bovis but Not M. tuberculosis in a Cattle Breed

2021 ◽  
Vol 8 ◽  
Author(s):  
Aude Remot ◽  
Florence Carreras ◽  
Anthony Coupé ◽  
Émilie Doz-Deblauwe ◽  
Maria L. Boschiroli ◽  
...  
Keyword(s):  
Mycobacterium Bovis ◽  
Close Contact ◽  
Animal Health ◽  
Mycobacterial Infection ◽  
Developed Countries ◽  
Host Cells ◽  
Economic Losses ◽  
Reference Laboratory ◽  
Type I ◽  
Interferon Pathway

Tuberculosis exacts a terrible toll on human and animal health. While Mycobacterium tuberculosis (Mtb) is restricted to humans, Mycobacterium bovis (Mb) is present in a large range of mammalian hosts. In cattle, bovine TB (bTB) is a noticeable disease responsible for important economic losses in developed countries and underestimated zoonosis in the developing world. Early interactions that take place between mycobacteria and the lung tissue early after aerosol infection govern the outcome of the disease. In cattle, these early steps remain poorly characterized. The precision-cut lung slice (PCLS) model preserves the structure and cell diversity of the lung. We developed this model in cattle in order to study the early lung response to mycobacterial infection. In situ imaging of PCLS infected with fluorescent Mb revealed bacilli in the alveolar compartment, in adjacent or inside alveolar macrophages, and in close contact with pneumocytes. We analyzed the global transcriptional lung inflammation signature following infection of PCLS with Mb and Mtb in two French beef breeds: Blonde d'Aquitaine and Charolaise. Whereas, lungs from the Blonde d'Aquitaine produced high levels of mediators of neutrophil and monocyte recruitment in response to infection, such signatures were not observed in the Charolaise in our study. In the Blonde d'Aquitaine lung, whereas the inflammatory response was highly induced by two Mb strains, AF2122 isolated from cattle in the UK and Mb3601 circulating in France, the response against two Mtb strains, H37Rv, the reference laboratory strain, and BTB1558, isolated from zebu in Ethiopia, was very low. Strikingly, the type I interferon pathway was only induced by Mb but not Mtb strains, indicating that this pathway may be involved in mycobacterial virulence and host tropism. Hence, the PCLS model in cattle is a valuable tool to deepen our understanding of early interactions between lung host cells and mycobacteria. It revealed striking differences between cattle breeds and mycobacterial strains. This model could help in deciphering biomarkers of resistance vs. susceptibility to bTB in cattle as such information is still critically needed for bovine genetic selection programs and would greatly help the global effort to eradicate bTB.

Induction of HOXA3 by PRRSV inhibits IFN-I response through negatively regulation of HO-1 transcription

2021 ◽  
Author(s):  
Yingtong Feng ◽  
Xuyang Guo ◽  
Hong Tian ◽  
Yuan He ◽  
Yang Li ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Gene Transcription ◽  
Immune Evasion ◽  
Molecular Mechanisms ◽  
Nuclear Translocation ◽  
Host Cells ◽  
Type I Interferons ◽  
Economic Losses ◽  
Heme Oxygenase 1 ◽  
Type I

Type I interferons (IFN-I) play a key role in the host defense against virus infection, but porcine reproductive and respiratory syndrome virus (PRRSV) infection does not effectively activate IFN-I response, and the underlying molecular mechanisms are poorly characterized. In this study, a novel transcription factor of the heme oxygenase-1 (HO-1) gene, homeobox A3 (HOXA3), was screened and identified. Here, we found that HOXA3 was significantly increased during PRRSV infection. We demonstrated that HOXA3 promotes PRRSV replication by negatively regulating the HO-1 gene transcription, which is achieved by regulating type I interferons (IFN-I) production. A detailed analysis showed that PRRSV exploits HOXA3 to suppress beta interferon (IFN-β) and IFN-stimulated gene (ISG) expression in host cells. We also provide direct evidence that the activation of IFN-I by HO-1 depends on its interaction with IRF3. Then we further proved that deficiency of HOXA3 promoted the HO-1-IRF3 interaction, and subsequently enhanced IRF3 phosphorylation and nuclear translocation in PRRSV-infected cells. These data suggest that PRRSV uses HOXA3 to negatively regulate the transcription of the HO-1 gene to suppress the IFN-I response for immune evasion. IMPORTANCE Porcine reproductive and respiratory syndrome (PRRS), caused by PRRSV, leads the pork industry worldwide to significant economic losses. HOXA3 is generally considered to be an important molecule in the process of body development and cell differentiation. Here, we found a novel transcription factor of the HO-1 gene, HOXA3, can negatively regulate the transcription of the HO-1 gene and play an important role in the suppression of IFN-I response by PRRSV. PRRSV induces the upregulation of HOXA3, which can negatively regulate HO-1 gene transcription, thereby weakening the interaction between HO-1 and IRF3 for inhibiting the type I IFN response. This study extends the function of HOXA3 to the virus field for the first time and provides new insights into PRRSV immune evasion mechanism.

scholarly journals Human, Animal and Planet Health for Complete Sustainability

Animals ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 1301
Author(s):  
Giuseppe Bertoni
Keyword(s):  
Human Health ◽  
Energy Use ◽  
Animal Health ◽  
Ghg Emissions ◽  
Good Health ◽  
Developed Countries ◽  
Economic Losses ◽  
Land Occupation ◽  
Food Borne ◽  
Negative Role

In order to discuss the concepts of animal health and sustainability, we must remind ourselves that ASF (animal source foods) can play a large role in human health, but that animals are assumed to have a negative role in the environment. Indeed, ASF can compromise human health, both in excess and in deficiency, so a proper amount of them is important. In addition, the environmental impact of farmed animals: land occupation, greenhouse gas (GHG) emissions, energy use and water utilization, acidification and eutrophication, must be minimized by reducing ASF consumption, as well as by increasing productivity. To achieve this, besides genetics, feeding and good management, the hygienic-sanitary and comfort conditions that ensure good health and welfare are essential. Impaired animal health can cause zoonosis and food-borne diseases and be responsible for economic and socio-economic losses (lower production-productivity and profitability) with consequential effects on the planet’s health too, and there are big differences between developing and developed countries. In the former, a prevalence of endemic infectious diseases and parasites is observed, and there is a lack of tools to restrain them; in the latter there is a decline of the above diseases, but an increase of stress-related diseases. Their reduction is equally important but requires a different strategy. In developing countries, the strategy should be to facilitate the availability of prevention and treatment means, while in developed countries it is necessary to use drugs correctly (to reduce residues, especially antimicrobials which are associated with important resistance risks to antibiotics) and improve the living conditions of animals (welfare).

scholarly journals Molecular Epidemiology of Tuberculosis in Cattle and Human Patients in ‎Bauchi and Gombe States, Northeastern Nigeria

2021 ◽  
Vol 18 (2) ◽  
pp. 23-32
Author(s):  
S. Ibrahim ◽  
S. Danbirni ◽  
A. S. Saidu ◽  
B. A. Usman ◽  
B. Y. Kaltungo ◽  
...  
Keyword(s):  
Public Health ◽  
Mycobacterium Tuberculosis ◽  
Mycobacterium Bovis ◽  
Molecular Typing ◽  
Animal Health ◽  
Economic Losses ◽  
Pcr Analysis ◽  
Surveillance Culture ◽  
Public Health Importance ◽  
Banding Patterns

Tuberculosis (TB) is recognized as the most important threat to human and animal health causing morbidity, mortality, and economic losses. A study was conducted to assess the epidemiology and zoonotic implications of TB in two states of northeastern Nigeria, using abattoir surveillance, culture, and molecular typing methods. The human sputum of in-patients from selected hospitals within the study areas was also collected, cultured, and subjected to molecular typing. Out of the 250 human sputa collected, 74 (29.6%) were positive for culture and 40(16%) were positive on Bioline® analysis. Also, of the 200 tissues collected, 62(32.5%) were AFB positive and 25(12.5%) were positive on culture and 18(9.0%) were positive on Bioline® analysis. All positive isolates on Bioline® analyses were further subjected to Genotype® MBTC analysis. A total of (n = 58) isolates; sputum (n=40) and tissue (n=18), identified as MBTC were further subjected to Genotype MBTC® Hain assay PCR analysis. in order to differentiate them into their various species. Of the MBTC isolates from the tissues, 8(4.0%) were found to be Mycobacterium bovis, 5(2.5%) were Mycobacterium tuberculosis and the remaining 5(2.5%) were unidentified using the standard banding patterns. The 40 MBTC from sputum showed 30 (75%) as Mycobacterium tuberculosis 6(15%) were Mycobacterium bovis, 3(7.5%) were Mycobacterium africanum and 1(0.4%) was unidentified using the standard banding patterns. In conclusion, the study revealed the public health importance of bTB in the study area. There is also the need for public health awareness programs on the zoonotic nature of bTB among the abattoir workers and the herdsmen.

scholarly journals A Single-Pass Type I Membrane Protein from the Apicomplexan Parasite Cryptosporidium parvum with Nanomolar Binding Affinity to Host Cell Surface

2021 ◽  
Vol 9 (5) ◽  
pp. 1015
Author(s):  
Tianyu Zhang ◽  
Xin Gao ◽  
Dongqiang Wang ◽  
Jixue Zhao ◽  
Nan Zhang ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Cell Surface ◽  
Host Cell ◽  
Binding Affinity ◽  
Cryptosporidium Parvum ◽  
Host Cells ◽  
Watery Diarrhea ◽  
Type I ◽  
Single Pass ◽  
Host Cell Surface

Cryptosporidium parvum is a globally recognized zoonotic parasite of medical and veterinary importance. This parasite mainly infects intestinal epithelial cells and causes mild to severe watery diarrhea that could be deadly in patients with weakened or defect immunity. However, its molecular interactions with hosts and pathogenesis, an important part in adaptation of parasitic lifestyle, remain poorly understood. Here we report the identification and characterization of a C. parvum T-cell immunomodulatory protein homolog (CpTIPH). CpTIPH is a 901-aa single-pass type I membrane protein encoded by cgd5_830 gene that also contains a short Vibrio, Colwellia, Bradyrhizobium and Shewanella (VCBS) repeat and relatively long integrin alpha (ITGA) N-terminus domain. Immunofluorescence assay confirmed the location of CpTIPH on the cell surface of C. parvum sporozoites. In congruence with the presence of VCBS repeat and ITGA domain, CpTIPH displayed high, nanomolar binding affinity to host cell surface (i.e., Kd(App) at 16.2 to 44.7 nM on fixed HCT-8 and CHO-K1 cells, respectively). The involvement of CpTIPH in the parasite invasion is partly supported by experiments showing that an anti-CpTIPH antibody could partially block the invasion of C. parvum sporozoites into host cells. These observations provide a strong basis for further investigation of the roles of CpTIPH in parasite-host cell interactions.

scholarly journals Sero-epidemiological survey of bluetongue disease in one-humped camel (Camelus dromedarius) in Kassala State, Eastern Sudan

2021 ◽  
Vol 74 (1) ◽  
Author(s):  
Molhima M. Elmahi ◽  
Mohammed O. Hussien ◽  
Abdel Rahim E. Karrar ◽  
Amira M. Elhassan ◽  
Abdel Rahim M. El Hussein
Keyword(s):  
Risk Factors ◽  
Potential Risk ◽  
Animal Health ◽  
Water Source ◽  
Economic Losses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Serum Samples ◽  
Cross Sectional ◽  
Potential Risk Factors ◽  
Eastern Sudan

Abstract Background Bluetongue (BT) is a vector-borne viral disease of ruminant and camelid species which is transmitted by Culicoides spp. The causative agent of BT is bluetongue virus (BTV) that belongs to genus Orbivirus of the family Reoviridae. The clinical disease is seen mainly in sheep but mostly sub-clinical infections of BT are seen in cattle, goats and camelids. The clinical reaction of camels to infection is usually not apparent. The disease is notifiable to the World Organization for Animal Health (OIE), causing great economic losses due to decreased trade and high mortality and morbidity rates associated with bluetongue outbreaks. The objective of this study was to investigate the seroprevalence of BTV in camels in Kassala State, Eastern Sudan and to identify the potential risk factors associated with the infection. A cross sectional study using a structured questionnaire survey was conducted during 2015–2016. A total of 210 serum samples were collected randomly from camels from 8 localities of Kassala State. The serum samples were screened for the presence of BTV specific immunoglobulin (IgG) antibodies using a competitive enzyme-linked immunosorbent assay (cELISA). Results Seropositivity to BTV IgG was detected in 165 of 210 camels’ sera accounting for a prevalence of 78.6%. Potential risk factors to BTV infection were associated with sex (OR = 0.061, p-value = 0.001) and seasonal river as water source for drinking (OR = 32.257, p-value = 0.0108). Conclusions Sex and seasonal river as water source for drinking were considered as potential risk factors for seropositivity to BTV in camels. The high prevalence of BTV in camels in Kassala State, Eastern Sudan, necessitates further epidemiological studies of BTV infection in camels and other ruminant species to better be able to control BT disease in this region.

scholarly journals Bacterial Cyclic Dinucleotides and the cGAS–cGAMP–STING Pathway: A Role in Periodontitis?

Pathogens ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 675
Author(s):  
Samira Elmanfi ◽  
Mustafa Yilmaz ◽  
Wilson W. S. Ong ◽  
Kofi S. Yeboah ◽  
Herman O. Sintim ◽  
...  
Keyword(s):  
Immune Response ◽  
Periodontal Disease ◽  
Innate Immune ◽  
Host Cells ◽  
Type I Interferons ◽  
Type I ◽  
Vaccine Adjuvants ◽  
Cyclic Dinucleotides ◽  
Sting Pathway

Host cells can recognize cytosolic double-stranded DNAs and endogenous second messengers as cyclic dinucleotides—including c-di-GMP, c-di-AMP, and cGAMP—of invading microbes via the critical and essential innate immune signaling adaptor molecule known as STING. This recognition activates the innate immune system and leads to the production of Type I interferons and proinflammatory cytokines. In this review, we (1) focus on the possible role of bacterial cyclic dinucleotides and the STING/TBK1/IRF3 pathway in the pathogenesis of periodontal disease and the regulation of periodontal immune response, and (2) review and discuss activators and inhibitors of the STING pathway as immune response regulators and their potential utility in the treatment of periodontitis. PubMed/Medline, Scopus, and Web of Science were searched with the terms “STING”, “TBK 1”, “IRF3”, and “cGAS”—alone, or together with “periodontitis”. Current studies produced evidence for using STING-pathway-targeting molecules as part of anticancer therapy, and as vaccine adjuvants against microbial infections; however, the role of the STING/TBK1/IRF3 pathway in periodontal disease pathogenesis is still undiscovered. Understanding the stimulation of the innate immune response by cyclic dinucleotides opens a new approach to host modulation therapies in periodontology.

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