Lipoproteins Are Potent Activators of Nuclear Factor Kappa B in Mammary Epithelial Cells and Virulence Factors in Mycoplasma bovis Mastitis

Schneider, Peleg; Brill, Re’ella; Schouten, Iftach; Nissim-Eliraz, Einat; Lysnyansky, Inna; Shpigel, Nahum Y.

doi:10.3390/microorganisms10112209

Cited by 3 publications

(4 citation statements)

References 78 publications

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“…Mycoplasma bovis strain PG45 (ATCC 25523 / NCTC 10131) (Hale et al, 1962;Wise et al, 2011) was used in this study and prepared for challenge in lactating mice as previously reported by us (Schneider et al, 2022). Bacteria were propagated at 37 o C in FF modified broth medium (Friis, 1975) supplemented with 0.5% (w/v) sodium pyruvate and 0.005% (w/v) phenol red.…”

Section: Bacterial Strainsmentioning

confidence: 99%

“…Experimental mastitis model systems were established in lactating BALB/c mice using intramammary (IMM) infusion of bacterial suspension to glands L4 and R4 (Figure 1A). We have used E. coli strain P4-NR and the type strain M. bovis PG45 as previously reported by us (Salamon et al, 2020;Schneider et al, 2022). Field strains of Strep.…”

Section: Establishment Of Murine Mastitis Model Systemmentioning

confidence: 99%

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Immune profiling of experimental murine mastitis reveals conserved response to mammary pathogenic Escherichia coli, Mycoplasma bovis, and Streptococcus uberis

et al. 2023

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Mastitis is one of the most prevalent and economically important diseases of dairy animals. The disease is caused by ascending bacterial infection through the teat canal. Among the most common mastitis-causing bacteria are Gram-negative coliforms, Gram-positive streptococci and staphylococci, and mycoplasma. The most prominent cellular hallmark of acute mammary infection is a massive recruitment of blood neutrophils into the tubular and alveolar milk spaces. The complex biological processes of leukocyte recruitment, activation, adhesion, and migration in the mammary gland remain largely elusive to date. While field research of mastitis in dairy animals contributed a lot to the development of mitigation, control, and even eradication programs, little progress was made toward understanding the molecular mechanisms underlying the pathogenesis of the disease. We report here experimental mastitis model systems in lactating mice challenged with field strains of common udder pathogens in dairy cows. We used these model systems to apply recently developed multiplex gene expression technology (Nanostring nCounter), which enabled us to study the expression of over 700 immune genes. Our analysis revealed a core of 100 genes that are similarly regulated and functionally or physically interacting in E. coli, M. bovis, and Strep uberis murine mastitis. Common significantly enriched gene sets include TNFɑ signaling via NFkB, Interferon gamma and alpha response, and IL6-JAK-STAT3 signaling. In addition, we show a significantly enriched expression of genes associated with neutrophil extracellular traps (NET) in glands challenged by the three pathogens. Ligand-receptor analysis revealed interactions shared by the three pathogens, including the interaction of the cytokines IL1β, IL1ɑ, and TNFɑ with their receptors, and proteins involved in immune cell recruitment such as complement C3 and ICAM1 (with CD11b), chemokines CCL3 and CCL4 (with CCR1), and CSF3 (with CSF3R). Taken together, our results show that mammary infection with E. coli, M. bovis, and Strep uberis culminated in the activation of a conserved core of immune genes and pathways including NET formation.

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Section: Bacterial Strainsmentioning

confidence: 99%

Section: Establishment Of Murine Mastitis Model Systemmentioning

confidence: 99%

Immune profiling of experimental murine mastitis reveals conserved response to mammary pathogenic Escherichia coli, Mycoplasma bovis, and Streptococcus uberis

et al. 2023

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“…M. bovis mastitis is characterized by massive recruitment of neutrophils into the milk spaces of the mammary gland ( 61 ). Similarly, M. bovis has been shown to stimulate production of neutrophils extracellular traps (NETs) and possess the membrane nuclease, MnuA which degrades the NETs through either exo- or endonuclease activity ( 38 , 62 ).…”

Section: Host Immune Responses Against Mycoplasma Bovis ...mentioning

confidence: 99%

“…M. bovis mastitis is characterized by massive recruitment of neutrophils into the milk spaces of the mammary gland (61).…”

Section: Host Immune Responses Against Mycoplasma Bovis Infection 41 ...mentioning

confidence: 99%

Mycoplasma bovis mastitis in dairy cattle

Gelgie,

Desai,

Gelalcha

et al. 2024

Front. Vet. Sci.

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Mycoplasma bovis has recently been identified increasingly in dairy cows causing huge economic losses to the dairy industry. M. bovis is a causative agent for mastitis, pneumonia, endometritis, endocarditis, arthritis, otitis media, and many other clinical symptoms in cattle. However, some infected cows are asymptomatic or may not shed the pathogen for weeks to years. This characteristic of M. bovis, along with the lack of adequate testing and identification methods in many parts of the world until recently, has allowed the M. bovis to be largely undetected despite its increased prevalence in dairy farms. Due to growing levels of antimicrobial resistance among wild-type M. bovis isolates and lack of cell walls in mycoplasmas that enable them to be intrinsically resistant to beta-lactam antibiotics that are widely used in dairy farms, there is no effective treatment for M. bovis mastitis. Similarly, there is no commercially available effective vaccine for M. bovis mastitis. The major constraint to developing effective intervention tools is limited knowledge of the virulence factors and mechanisms of the pathogenesis of M. bovis mastitis. There is lack of quick and reliable diagnostic methods with high specificity and sensitivity for M. bovis. This review is a summary of the current state of knowledge of the virulence factors, pathogenesis, clinical manifestations, diagnosis, and control of M. bovis mastitis in dairy cows.

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Bioactive Compounds and Probiotics Mitigate Mastitis by Targeting NF-κB Signaling Pathway

Khan,

Li,

Wang

et al. 2024

Biomolecules

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Mastitis is a significant inflammatory condition of the mammary gland in dairy cows. It is caused by bacterial infections and leads to substantial economic losses worldwide. The disease can be either clinical or sub-clinical and presents challenges such as reduced milk yield, increased treatment costs, and the need to cull affected cows. The pathogenic mechanisms of mastitis involve the activation of Toll-like receptors (TLRs), specifically TLR2 and TLR4. These receptors play crucial roles in recognizing pathogen-associated molecular patterns (PAMPs) and initiating immune responses through the NF-κB signaling pathway. Recent in vitro studies have emphasized the importance of the TLR2/TLR4/NF-κB signaling pathway in the development of mastitis, suggesting its potential as a therapeutic target. This review summarizes recent research on the role of the TLR2/TLR4/NF-κB signaling pathway in mastitis. It focuses on how the activation of TLRs leads to the production of proinflammatory cytokines, which, in turn, exacerbate the inflammatory response by activating the NF-κB signaling pathway in mammary gland tissues. Additionally, the review discusses various bioactive compounds and probiotics that have been identified as potential therapeutic agents for preventing and treating mastitis by targeting TLR2/TLR4/NF-κB signaling pathway. Overall, this review highlights the significance of targeting the TLR2/TLR4/NF-κB signaling pathway to develop effective therapeutic strategies against mastitis, which can enhance dairy cow health and reduce economic losses in the dairy industry.

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Lipoproteins Are Potent Activators of Nuclear Factor Kappa B in Mammary Epithelial Cells and Virulence Factors in Mycoplasma bovis Mastitis

Cited by 3 publications

References 78 publications

Immune profiling of experimental murine mastitis reveals conserved response to mammary pathogenic Escherichia coli, Mycoplasma bovis, and Streptococcus uberis

Immune profiling of experimental murine mastitis reveals conserved response to mammary pathogenic Escherichia coli, Mycoplasma bovis, and Streptococcus uberis

Mycoplasma bovis mastitis in dairy cattle

Bioactive Compounds and Probiotics Mitigate Mastitis by Targeting NF-κB Signaling Pathway

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