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Gene Expression Study of Host and Mycobacterium tuberculosis Interactions in the Manifestation of Acute Tuberculosis

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Abstract

Mycobacterium tuberculosis (M.tb) could induce type IV hypersensitivity. The chemotaxis of the leukocytes toward the site of infection and producing matrix metalloproteinases (MMPs) are key factors in the immune pathogenesis of tuberculosis (TB). Mononuclear cells were isolated from bronchoalveolar lavage (BAL) specimens, and the target from genomic DNA was used for qPCR TB diagnosis and cDNA for specific RT-qPCR gene expression. The subjects were then classified into TB+ and TB− groups, and the expression levels of CFP-10, ESAT-6, CCR1, CCR12 and MMP3,9 were evaluated. The mean level of CCR1 expression in TB+ and TB− patients’ BAL was 1.71 ± 0.78 and 0.5 ± 0.22, respectively, which was statistically different (p = 0.01). The CCR2 level, in TB+ (2.07 ± 1.4), was higher than in TB− patients (1.42 ± 0.89, p = 0.01). The MMP9 expression in TB+ was 2.56 ± 0.68, also higher than in TB− patients (1.13 ± 0.35), while MMP3 was lower in TB+ (0.22 ± 0.09) than in TB− (0.64 ± 0.230, p = 0.05). The CCR2/CCR1 and MMP3/MMP9 balance in TB+ were reduced, compared to the TB−. The CFP-10 and ESAT-6 were highly expressed in TB+ patients. The CFP-10 expression had a strong negative correlation with albumin (r =  − 0.93, p = 0.001), and a negative correlation with neutrophil (r =  − 0.444, p = 0.1 with 90% CI). The MMP-9 expression showed a positive correlation with WBC count (r = 0.61, p = 0.02), in TB+, and had a negative correlation with BMI (r = 0.59, p = 0.02) in TB−. The M.tb CFP-10 might be implicated in lowering CCR2 and MMP3 expression in favour of M.tb dissemination. Moreover, the balance of CCR2/CCR1 and MMP3/MMP9 can be used as prognostic factors in the severity of TB.

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Data Availability

All data generated or analysed during this study are included in this manuscript and are available from the corresponding author upon reasonable request.

Abbreviations

APCs:

Antigen-presenting cells

BAL:

Bronchoalveolar lavage

CCR1:

C-C chemokine receptor type 1

CCR2:

C-C chemokine receptor type 1

CFP-10:

Culture filtrate protein 10 kDa

ESAT-6:

Early secretory antigenic target 6 kDa

M.tb :

Mycobacterium tuberculosis

MMP:

Matrix metalloproteinases

PBMCs:

Peripheral blood mononuclear cells

qPCR:

Real-time PCR

RT-qPCR:

Reverse transcription qPCR

TB:

Tuberculosis

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Funding

This study was subjected to an MSc thesis in Medical Microbiology and financially supported by the Vice-Chancellor for Research and Technology, Mashhad University of Medical Sciences, Mashhad, Iran, under grants MUMS. 930690 and MUMS. 941165.

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Author notes

  1. Shadi Abbasnia, Sara Hajimiri and Mozhdeh Jafari Rad contributed equally to this work and have equal credit.

Authors and Affiliations

  1. Immunology Research Center, Inflammation and Inflammatory Diseases Division, Mashhad University of Medical Sciences, Mashhad, Iran

    Shadi Abbasnia, Mozhdeh Jafari Rad, Nazila Ariaee, Fatemeh Sadat Mohammadi & Seyed Abdolrahim Rezaee

  2. Antimicrobial Resistance Research Center, Bu-Ali Research Institute, Mashhad University of Medical Sciences, Mashhad, Iran

    Sara Hajimiri, Mohammad Derakhshan, Saeid Amel Jamehdar & Kiarash Ghazvini

  3. Department of Microbiology and Virology, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Sara Hajimiri, Mohammad Derakhshan, Saeid Amel Jamehdar & Kiarash Ghazvini

  4. Blood Borne Infections Research Center, Academic Center for Education, Culture and Research (ACECR), Razavi Khorasan, Mashhad, Iran

    Arman Mosavat

  5. Department of Internal Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

    Amir Mohamad Hashem Asnaashari

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Contributions

SA, SH and FM collected the samples and performed the experiments. HA, as a pulmonologist, monitored the patients and took the BAL. NA, SMJ and AM compiled the data and prepared the draft. MD and SAJ were the co-supervisors. KG and SAR supervised the study. SAR planned the study, did the statistics and revised the manuscript. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Seyed Abdolrahim Rezaee.

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Research Involving Human Participants and Informed consent

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. This study was reviewed, approved and supervised by the Biomedical Research Ethics Committee of the Mashhad University of Medical Sciences, Mashhad, Iran (IR.MUMS.REC.930690 and IR.MUMS.REC. 941165), and written informed consent forms were obtained and signed by all participants.

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Abbasnia, S., Hajimiri, S., Jafari Rad, M. et al. Gene Expression Study of Host and Mycobacterium tuberculosis Interactions in the Manifestation of Acute Tuberculosis. Appl Biochem Biotechnol 195, 3641–3652 (2023). https://doi.org/10.1007/s12010-023-04329-9

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