Mycoplasma gallisepticum: influence of cell invasiveness on the outcome of experimental infection in chickens

Much, P

doi:10.1016/s0928-8244(02)00378-4

Cited by 13 publications

(15 citation statements)

References 21 publications

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“…In view of the prevailing scenario, we tried to investigate whether M. agalactiae has the capacity to enter, survive and exit the eukaryotic host cells in a viable state, as this could explain the chronic, persistent and difficult-to-eradicate nature of its infections in spite of long antibiotic therapies. This phenomenon may also allow it to reach more favorable host niches by crossing the epithelial barrier as cell invasion is often considered a major factor for systemic spread ( Cieri et al, 2002; Much et al, 2002 ). Here, we provide evidence for the first time that M. agalactiae is able to invade eukaryotic host cells whereby quantitative results are supported by the qualitative double immunofluorescence assay.…”

Section: Introductionmentioning

confidence: 99%

In vitro and in vivo cell invasion and systemic spreading of Mycoplasma agalactiae in the sheep infection model

Hegde¹,

Hegde²,

Spergser³

et al. 2014

International Journal of Medical Microbiology

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Generally regarded as extracellular pathogens, molecular mechanisms of mycoplasma persistence, chronicity and disease spread are largely unknown. Mycoplasma agalactiae, an economically important pathogen of small ruminants, causes chronic infections that are difficult to eradicate. Animals continue to shed the agent for several months and even years after the initial infection, in spite of long antibiotic treatment. However, little is known about the strategies that M. agalactiae employs to survive and spread within an immunocompetent host to cause chronic disease. Here, we demonstrate for the first time its ability to invade cultured human (HeLa) and ruminant (BEND and BLF) host cells. Presence of intracellular mycoplasmas is clearly substantiated using differential immunofluorescence technique and quantitative gentamicin invasion assays. Internalized M. agalactiae could survive and exit the cells in a viable state to repopulate the extracellular environment after complete removal of extracellular bacteria with gentamicin. Furthermore, an experimental sheep intramammary infection was carried out to evaluate its systemic spread to organs and host niches distant from the site of initial infection. Positive results obtained via PCR, culture and immunohistochemistry, especially the latter depicting the presence of M. agalactiae in the cytoplasm of mammary duct epithelium and macrophages, clearly provide the first formal proof of M. agalactiae's capability to translocate across the mammary epithelium and systemically disseminate to distant inner organs. Altogether, the findings of these in vitro and in vivo studies indicate that M. agalactiae is capable of entering host cells and this might be the strategy that it employs at a population level to ward off the host immune response and antibiotic action, and to disseminate to new and safer niches to later egress and once again proliferate upon the return of favorable conditions to cause persistent chronic infections.

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Section: Introductionmentioning

confidence: 99%

In vitro and in vivo cell invasion and systemic spreading of Mycoplasma agalactiae in the sheep infection model

Hegde¹,

Hegde²,

Spergser³

et al. 2014

International Journal of Medical Microbiology

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“…This pathogen is known to invade, survive and multiply inside a variety of non-phagocytic cells such as chicken RBCs, HeLa cells, and chicken fibroblasts, [4] – [9] . In addition, M. gallisepticum is known to colonize many extra-pulmonary tissues including blood, heart, spleen, liver and brain [4] , [5] , [7] , [8] , [10] . Indikova et al (2013) suggested that invasion may occur at the air sac, where the mucosal barrier is quite thin [7] .…”

Section: Introductionmentioning

confidence: 99%

Mycoplasma gallisepticum Lipid Associated Membrane Proteins Up-regulate Inflammatory Genes in Chicken Tracheal Epithelial Cells via TLR-2 Ligation through an NF-κB Dependent Pathway

2014

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Mycoplasma gallisepticum-mediated respiratory inflammation in chickens is associated with accumulation of leukocytes in the tracheal submucosa. However the molecular mechanisms underpinning these changes have not been well described. We hypothesized that the initial inflammatory events are initiated upon ligation of mycoplasma lipid associated membrane proteins (LAMP) to TLRs expressed on chicken tracheal epithelial cells (TEC). To test this hypothesis, live bacteria or LAMPs isolated from a virulent (Rlow) or a non-virulent (Rhigh) strain were incubated with primary TECs or chicken tracheae ex vivo. Microarray analysis identified up-regulation of several inflammatory and chemokine genes in TECs as early as 1.5 hours post-exposure. Kinetic analysis using RT-qPCR identified the peak of expression for most genes to be at either 1.5 or 6 hours. Ex-vivo exposure also showed up-regulation of inflammatory genes in epithelial cells by 1.5 hours. Among the commonly up-regulated genes were IL-1β, IL-6, IL-8, IL-12p40, CCL-20, and NOS-2, all of which are important immune-modulators and/or chemo-attractants of leukocytes. While these inflammatory genes were up-regulated in all four treatment groups, Rlow exposed epithelial cells both in vitro and ex vivo showed the most dramatic up-regulation, inducing over 100 unique genes by 5-fold or more in TECs. Upon addition of a TLR-2 inhibitor, LAMP-mediated gene expression of IL-1β and CCL-20 was reduced by almost 5-fold while expression of IL-12p40, IL-6, IL-8 and NOS-2 mRNA was reduced by about 2–3 fold. Conversely, an NF-κB inhibitor abrogated the response entirely for all six genes. miRNA-146a, a negative regulator of TLR-2 signaling, was up-regulated in TECs in response to either Rlow or Rhigh exposure. Taken together we conclude that LAMPs isolated from both Rhigh and Rlow induced rapid, TLR-2 dependent but transient up-regulation of inflammatory genes in primary TECs through an NF-κB dependent pathway.

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“…However, there is now accumulating evidence that some mycoplasmas can invade non-phagocytic cells, and M. gallisepticum appears to be one such organism (Winner et al, 2000). The invasiveness of the strain of M. gallisepticum was reported to influence the outcome of experimental infections in chickens (Much et al, 2002) and a more invasive strain was found in the heart, brain, liver and kidney of infected birds, indicating haematogenous spread. The authors speculated that expression of the gapA gene might be a crucial factor in influencing cell invasion, because a highly passaged, avirulent derivative of the invasive strain had an irreversible mutation in this gene, which prohibited expression.…”

Section: Invasionmentioning

confidence: 99%

Poultry mycoplasmas: sophisticated pathogens in simple guise

Bradbury¹

2005

British Poultry Science

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Mycoplasmas are a genus within the class Mollicutes (trivial name mollicutes), which are the smallest known prokaryotes capable of self-replication. They have a very small genome, and have evolved to this 'minimalist' status by losing non-essential genes, including those involved in cell wall synthesis. The mollicutes exploit their limited genetic material to the maximum and many are successful pathogens in man, animals, birds and plants. Most of those of veterinary importance are in the genus Mycoplasma and include 4 poultry pathogens of economic importance: Mycoplasma gallisepticum, Mycoplasma synoviae, Mycoplasma meleagridis and Mycoplasma iowae. The pathogenetic mechanisms of mycoplasmas are not fully understood, but they are successful pathogens because they can enter the host and multiply, evade the defence mechanisms, cause damage and escape to infect new hosts. M. gallisepticum is one of several motile species and possesses a terminal tip structure that mediates adherence to its target tissues. For some species, including M. gallisepticum, some of the organisms may become intracellular. Some Mycoplasma species, including the pathogenic poultry species, have a remarkable ability to vary their major surface antigens, a mechanism that is thought to help them to persist in their host by evading the immune response. The molecular and cellular events that lead to the development of lesions and clinical disease are still obscure. Some lesions appear to be the result of indirect damage from the host's inflammatory and cellular responses. Despite short survival times in the environment, mycoplasmas are able to transmit successfully to new hosts. In poultry flocks there is both horizontal and vertical transmission, the former being encouraged by intensive husbandry and stress factors. Establishing the pathways of transmission and the possible role of other birds, such as game and wild birds, as intermediate vectors between poultry flocks is now greatly aided by the availability of modern molecular methods for strain typing.

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Mycoplasma gallisepticum: influence of cell invasiveness on the outcome of experimental infection in chickens

Cited by 13 publications

References 21 publications

In vitro and in vivo cell invasion and systemic spreading of Mycoplasma agalactiae in the sheep infection model

In vitro and in vivo cell invasion and systemic spreading of Mycoplasma agalactiae in the sheep infection model

Mycoplasma gallisepticum Lipid Associated Membrane Proteins Up-regulate Inflammatory Genes in Chicken Tracheal Epithelial Cells via TLR-2 Ligation through an NF-κB Dependent Pathway

Poultry mycoplasmas: sophisticated pathogens in simple guise

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