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Volume 71, Issue 11

Clinical isolates of with different genotypes exhibit distinct host macrophage responses Open Access

Abstract

. (), the causative agent of tuberculosis, can survive as an intracellular parasite after entering macrophages via phagocytosis. strains are genotypically distinct and engage in diverse pathogen–host interactions, with different host immune responses triggered by different strains. Importantly, differences in intracellular accumulation and triggering of host macrophage responses during early infection stages are key determinants that shape the final outcomes of host innate immune responses to different strains.

. Clinical strains with different genotypes elicit different host innate immune responses .

. This work aimed to compare host innate immune responses elicited by genotypically diverse, clinically derived strains .

. RAW264.7 cells were infected with three lineage 2 and lineage 4 clinically derived strains and strain H37Rv. Strains were evaluated for differences in intracellular growth, induction of macrophage apoptosis, and induction of expression of proinflammatory cytokines and associated pattern recognition receptors.

. Highly variable cytokine profiles were observed subsequent to RAW264.7 cell infection with the different strains. The Beijing genotype strain, a modern Beijing strain belonging to lineage 2, induced milder host proinflammatory responses and less apoptosis and exhibited greater intracellular growth as compared to the other strains. Moreover, mRNA expression levels of in Beijing and MANU2 genotype strains exceeded corresponding levels obtained for the T1 genotype strain. Meanwhile, mRNA expression levels of toll-like receptor (TLR)-encoding genes and in macrophages infected with the Beijing genotype strain were higher than corresponding levels observed in MANU2 genotype strain-infected macrophages.

. The higher intracellular survival rate and lower level of host cell apoptosis associated with macrophage infection with the Beijing genotype strain indicated greater virulence of this strain relative to that of the other strains. Furthermore, immune responses induced by the Beijing genotype strain were unique in that this strain induced a weaker inflammatory response than was induced by T1 or MANU2 genotype strains. Nevertheless, additional evidence is needed to confirm that Beijing genotype strains possess greater virulence than strains with other genotypes.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): cytokines , genotype , innate immunity and Mycobacterium tuberculosis
Funding
This study was supported by the:
  • Scientific Research Project of Beijing Educational Committee (Award KM202010025001)
  • the Research Capability Promotion Project of Beijing TB and Thoracic Tumor Research Institute (Award KJ2021CX010)
    • Principle Award Recipient: YiLiu
  • the Capital Medical Development Special Foundation (Award 2020-2-1042)
    • Principle Award Recipient: ChuanYouLi
  • Beijing Key Clinical Speciality Project (Award 20201214)
    • Principle Award Recipient: ShenjieTang
© 2022 The Authors
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2022-11-28
2024-04-18
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Clinical isolates of Mycobacterium tuberculosis with different genotypes exhibit distinct host macrophage responses in vitro
J. Med. Microbiol. 71, 001604 (2022); https://doi.org/10.1099/jmm.0.001604
/content/journal/jmm/10.1099/jmm.0.001604
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