Multinucleated Giant Cell Formation as a Portal to Chronic Bacterial Infections

Stockton, Jacob L; Torres, Alfredo G.

doi:10.3390/microorganisms8111637

Cited by 20 publications

(13 citation statements)

References 56 publications

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“…These results agree with (31) that these lesions are due to progression of infection with pathogenic bacteria, leading to an increase in the number of macrophages and stimulation of fibroblast activity that resulted in damage of alveolar epithelium decreasing in secretary activity of it. Further, multiplication of connective tissue to the large ductal lumen and glandular intestinal tissues (32), at the last stage of mastitis, there was thickening of the alveolar wall which become cornified and hypertrophied and this agreement with (33,34), who mention similar changes in the mammary gland.…”

Section: Discussionsupporting

confidence: 71%

Histopathological and histochemical study of mastitis in sheep

Rahawi

Al-Sabaawy

Ismail

2022

IJVS

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Ovine mastitis is considered one of the problems that cause economic losses through its impact on milk production, which is unfit for human consumption. The current study aimed to shed light on mastitis in sheep in different areas of Mosul city. The results of the recent study showed the presence of mammary macroscopic and microscopic changes. Macroscopic changes were represented by the large size of the udder and changes in the color and texture, as well as clarity of sloughing and desquamation of the skin with clear exudation, especially in advanced cases. On the other hand, other samples showed the presence of hard nodules on the udders. In contrast, the histological changes represented by degenerative and necrotic changes 3.5%, and 21.4% of the sample appeared to suffer from liquefactive necrosis and abscesses infiltrated with inflammatory cells, 25% of the samples infected with granulomatous mastitis (nodular mastitis), other models showed that the udder infected with atrophy and metaplasia in the rate of 21%, thickening of the blood vessel wall with clot represented 14.2% and the deposition of calcium salt was 14.2%. The current study concludes that mastitis in sheep is widespread in sheep raised in different areas of Mosul city.

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Section: Discussionsupporting

confidence: 71%

Histopathological and histochemical study of mastitis in sheep

Rahawi

Al-Sabaawy

Ismail

2022

IJVS

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“…B. pseudomallei has been shown to spread into nearby host cells and induce those cells to form MNGC [ 6 ]. The formation of MNGC assists B. pseudomallei to survive under potentially harmful conditions, such as in the presence of antimicrobial agents or antibodies [ 30 ]. This characteristic appears to be related to pathogenicity of B. pseudomallei [ 31 ].…”

Section: Resultsmentioning

confidence: 99%

Burkholderia pseudomallei pathogenesis in human skin fibroblasts: A Bsa type III secretion system is involved in the invasion, multinucleated giant cell formation, and cellular damage

et al. 2022

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Burkholderia pseudomallei—a causative agent of melioidosis that is endemic in Southeast Asia and Northern Australia—is a Gram-negative bacterium transmitted to humans via inhalation, inoculation through skin abrasions, and ingestion. Melioidosis causes a range of clinical presentations including skin infection, pneumonia, and septicemia. Despite skin infection being one of the clinical symptoms of melioidosis, the pathogenesis of B. pseudomallei in skin fibroblasts has not yet been elucidated. In this study, we investigated B. pseudomallei pathogenesis in the HFF-1 human skin fibroblasts. On the basis of co-culture assays between different B. pseudomallei clinical strains and the HFF-1 human skin fibroblasts, we found that all B. pseudomallei strains have the ability to mediate invasion, intracellular replication, and multinucleated giant cell (MNGC) formation. Furthermore, all strains showed a significant increase in cytotoxicity in human fibroblasts, which coincides with the augmented expression of matrix metalloproteinase-2. Using B. pseudomallei mutants, we showed that the B. pseudomallei Bsa type III secretion system (T3SS) contributes to skin fibroblast pathogenesis, but O-polysaccharide, capsular polysaccharide, and short-chain dehydrogenase metabolism do not play a role in this process. Taken together, our findings reveal a probable connection for the Bsa T3SS in B. pseudomallei infection of skin fibroblasts, and this may be linked to the pathogenesis of cutaneous melioidosis.

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“…However, their recognition, fusion, and activation signaling pathways are not completely understood. Macrophages fuse together to form multinucleated giant cells (MGC) in granuloma bodies, which are associated with various pathological conditions following HIV, tuberculosis, and herpes infection (Stockton and Torres, 2020 ). Interestingly, we also observed multinucleated giant cell-like structures in macrophage cultures infected with Ms_Rv1509.…”

Section: Resultsmentioning

confidence: 99%

Expression of a unique M. tuberculosis DNA MTase Rv1509 in M. smegmatis alters the gene expression pattern and enhances virulence

Manjunath,

Ahmad,

Samal

et al. 2024

Front. Microbiol.

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Mycobacterium tuberculosis (M. tb) genome encompasses 4,173 genes, about a quarter of which remain uncharacterized and hypothetical. Considering the current limitations associated with the diagnosis and treatment of tuberculosis, it is imperative to comprehend the pathomechanism of the disease and host-pathogen interactions to identify new drug targets for intervention strategies. Using in-silico comparative genome analysis, we identified one of the M. tb genes, Rv1509, as a signature protein exclusively present in M. tb. To explore the role of Rv1509, a likely methyl transferase, we constructed a knock-in Mycobacterium smegmatis (M. smegmatis) constitutively expressing Rv1509 (Ms_Rv1509). The Ms_Rv1509 led to differential expression of many transcriptional regulator genes as assessed by RNA-seq analysis. Further, in-vitro and in-vivo studies demonstrated an enhanced survival of Ms_Rv1509 inside the host macrophages. Ms_Rv1509 also promoted phagolysosomal escape inside macrophages to boost bacterial replication and dissemination. In-vivo infection studies revealed that Ms_Rv1509 survives better than BCG and causes pathological manifestations in the pancreas after intraperitoneal infection. Long-time survival of Ms_Rv1509 resulted in lymphocyte migration, increased T regulatory cells, giant cell formation, and likely granuloma formation in the pancreas, pointing toward the role of Rv1509 in M. tb pathogenesis.

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Multinucleated Giant Cell Formation as a Portal to Chronic Bacterial Infections

Cited by 20 publications

References 56 publications

Histopathological and histochemical study of mastitis in sheep

Histopathological and histochemical study of mastitis in sheep

Burkholderia pseudomallei pathogenesis in human skin fibroblasts: A Bsa type III secretion system is involved in the invasion, multinucleated giant cell formation, and cellular damage

Expression of a unique M. tuberculosis DNA MTase Rv1509 in M. smegmatis alters the gene expression pattern and enhances virulence

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