Mutations in ace2 gene modulate cytokine levels and alter immune responses in Mycobacterium tuberculosis and SARS-CoV-2 co-infection: a Cameroonian cohort.
| Title: | Mutations in ace2 gene modulate cytokine levels and alter immune responses in Mycobacterium tuberculosis and SARS-CoV-2 co-infection: a Cameroonian cohort. |
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| Authors: | Kameni MN; Molecular Diagnostics Research Group, Biotechnology Centre-University of Yaounde I (MDRG-BTC-UYI), Yaounde, Cameroon.; Department of Microbiology, University of Yaounde I, Yaounde, Cameroon.; Translational Health Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.; Tchoupe EB; Molecular Diagnostics Research Group, Biotechnology Centre-University of Yaounde I (MDRG-BTC-UYI), Yaounde, Cameroon.; Department of Clinical Biochemistry, Faculty of Medicine and Biomedical Science, University of Yaounde I, Yaounde, Cameroon.; Kamdem SD; Molecular Diagnostics Research Group, Biotechnology Centre-University of Yaounde I (MDRG-BTC-UYI), Yaounde, Cameroon.; Department of Pathology, School of Medicine, University of Utah, Salt Lake City, UT, United States.; Bhalla N; Translational Health Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.; Assam Assam JP; Department of Microbiology, University of Yaounde I, Yaounde, Cameroon.; Tepa AN; Molecular Diagnostics Research Group, Biotechnology Centre-University of Yaounde I (MDRG-BTC-UYI), Yaounde, Cameroon.; Neba FR; Molecular Diagnostics Research Group, Biotechnology Centre-University of Yaounde I (MDRG-BTC-UYI), Yaounde, Cameroon.; Nanda RK; Translational Health Group, International Centre for Genetic Engineering and Biotechnology, New Delhi, India.; Awuah AA; Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana.; Department of Infectious Diseases Epidemiology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.; College of Health Sciences, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana.; Amuasi JH; Kumasi Centre for Collaborative Research in Tropical Medicine, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana.; Department of Infectious Diseases Epidemiology, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.; College of Health Sciences, Kwame Nkrumah University of Science and Technology (KNUST), Kumasi, Ghana.; Netongo PM; Molecular Diagnostics Research Group, Biotechnology Centre-University of Yaounde I (MDRG-BTC-UYI), Yaounde, Cameroon.; Biology Program, School of Science, Navajo Technical University, Crownpoint, NM, United States.; Department of Biochemistry, University of Yaounde I, Yaounde, Cameroon. |
| Source: | Frontiers in immunology [Front Immunol] 2025 Mar 24; Vol. 16, pp. 1533213. Date of Electronic Publication: 2025 Mar 24 (Print Publication: 2025). |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Frontiers Research Foundation] Country of Publication: Switzerland NLM ID: 101560960 Publication Model: eCollection Cited Medium: Internet ISSN: 1664-3224 (Electronic) Linking ISSN: 16643224 NLM ISO Abbreviation: Front Immunol Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: [Lausanne : Frontiers Research Foundation] |
| MeSH Terms: | COVID-19*/immunology ; COVID-19*/genetics ; Angiotensin-Converting Enzyme 2*/genetics ; SARS-CoV-2*/immunology ; Mycobacterium tuberculosis*/immunology ; Cytokines*/blood ; Cytokines*/immunology ; Serine Endopeptidases*/genetics ; Coinfection*/immunology ; Coinfection*/genetics ; Tuberculosis*/immunology ; Tuberculosis*/genetics; Humans ; Polymorphism, Single Nucleotide ; Female ; Male ; Middle Aged ; Adult ; Cameroon ; Mutation ; Cohort Studies ; Genetic Predisposition to Disease ; Aged ; Genotype |
| Abstract: | Introduction: SARS-CoV-2 and Mycobacterium tuberculosis (Mtb) share similarities in their modes of transmission, pathophysiological symptoms, and clinical manifestations. An imbalance in the immune response characterised by elevated levels of some inflammatory cytokines caused by tuberculosis (TB) and COVID-19 may increase the risk of developing a severe disease-like condition. It has been reported that TB increases the expression levels of Ace2 (angiotensin converting enzyme 2) and Tmprss2 (transmembrane protease serine 2) proteins, which are essential for COVID-19 pathogenesis. Single nucleotide polymorphisms (SNPs) variants of ace2 and tmprss2 genes can impact virus and host-cell interactions and alter immune responses by modulating cytokine production. This may modify the susceptibility and/or severity in COVID-19-infected people. The role of SNPs in ace2 and tmprss2 in relation to Mtb and SARS-CoV-2 co-infection is relatively underexplored.; Method: In this study, genotype frequency of 10 SNPs of ace2 and 03 SNPs of tmprss2 genes in a Cameroonian cohort consisting of COVID-19-positive (n = 31), TB-positive (n = 43), TB-COVID-19 co-infected (n = 21), and a control group (n = 24) were studied. The immune response was estimated by quantitating inflammatory cytokine levels alongside self-reported and clinically diagnosed symptoms. The relationship between specific genetic mutations in these ace2 gene SNPs and their impact on cytokine expression levels in Mtb and SARS-CoV-2 co-infected patients was investigated.; Results: We identified wild-type, heterozygous, and double-mutant genotypes in seven SNPs (rs2285666, rs6632677, rs4646116, rs4646140, rs147311723, rs2074192 and rs4646142) in ace2 gene, which showed significant variations in distribution across the study groups. Our most significant findings include the association of double mutant alleles (AA) of rs4646140 and rs2074192 in the ace2 gene with decreased IL-6 and IL-2 expression levels respectively in TB-COVID-19 participants. Also, the double mutant alleles (AA) of rs4646116 were responsible for increased expression level of IL-2 in TB-COVID-19 patients. Additionally, elevated serum levels of AST, urea, and D-dimer, as well as increased plasma concentrations of IL-10, IFN-γ, and TNF-α, have been associated with co-infections involving Mtb and SARS-CoV-2.; Conclusion: These biomarkers may reflect the complex interplay between the two pathogens and their impact on host immune responses and disease progression. This study highlights the critical role of genetic and immunological factors in shaping altered immune responses during co-infections involving Mtb and SARS-CoV-2. By elucidating these factors, the findings provide a foundation for a deeper understanding of host-pathogen interactions and their implications for disease progression and outcomes. Furthermore, this research has the potential to drive advancements in diagnostic approaches enabling more accurate detection and monitoring of co-infections.; (Copyright © 2025 Kameni, Tchoupe, Kamdem, Bhalla, Assam Assam, Tepa, Neba, Nanda, Awuah, Amuasi and Netongo.) |
| Competing Interests: | The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. |
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| Contributed Indexing: | Keywords: COVID - 19; Mycobacterium tuberculosis; SARS-CoV-2; SNPs; ace2; immune response; tmprss2; tuberculosis |
| Substance Nomenclature: | EC 3.4.17.23 (Angiotensin-Converting Enzyme 2); EC 3.4.17.23 (ACE2 protein, human); EC 3.4.21.- (TMPRSS2 protein, human); 0 (Cytokines); EC 3.4.21.- (Serine Endopeptidases) |
| Entry Date(s): | Date Created: 20250408 Date Completed: 20250409 Latest Revision: 20250409 |
| Update Code: | 20260130 |
| PubMed Central ID: | PMC11973369 |
| DOI: | 10.3389/fimmu.2025.1533213 |
| PMID: | 40196114 |
| Database: | MEDLINE |
Journal Article