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AIMS Allergy and Immunology

2026, Volume 10, Issue 2: 116-130. doi: 10.3934/Allergy.2026010
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Review

Clinical efficacies of immune-cell-targeted interventions a revolutionary era in host immune gene expression in MRSA infections

  • 1.
    Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  • 2.
    Department of Medical Microbiology and Virology, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
  • 3.
    Department of Immunology, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran
  • 4.
    Department of Medical Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  • 5.
    Department of Immunology, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran
  • 6.
    Department of Immunology, School of Medicine, Kerman University of Medical Sciences, Kerman, Iran
  • 7.
    Department of Immunology, School of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
  • 8.
    Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
  • Published: 25 June 2026
  • Background and aims 

    Methicillin-resistant Staphylococcus aureus (MRSA) remains a major cause of healthcare-associated infections worldwide, frequently progressing to bacteremia, and with high mortality rates, particularly in patients with recurrent or persistent infections involving skin/soft tissue and the bloodstream. Traditional antibiotic therapies are increasingly limited by MDR and immune evasion mechanisms. This review synthesized host immune transcriptomic changes during MRSA infections and evaluated the clinical translational potential of next-generation vaccines developed after 2020.

    Methods 

    Relevant searches were conducted in PubMed, Embase, and Web of Science (2020–2025) using combinations of terms related to MRSA, host immune gene expression, transcriptomics, scRNA-seq, and next-generation vaccines. Eligible studies included original research and reviews reporting primary data on immune transcriptomics or vaccine immunogenicity/protective efficacy in MRSA infections.

    Results 

    MRSA infection triggers strong innate immune activation (TLR2/NOD2 signaling, IL-1β/IL-6/TNF-α upregulation) and heterogeneous macrophage polarization (M1 proinflammatory vs. M2 immunosuppressive phenotypes), alongside adaptive Th1/Th17 responses that are undermined by superantigens, IL-10 hypersecretion, and PD-1-mediated exhaustion. Multivalent mRNA-LNP vaccines encoding ClfA-Hla-IsdB fusions induce strong Th1/Th17 immunity, ~80% opsonophagocytic killing activity, 90% reduction in bacterial load, and 75% survival in murine sepsis models.

    Conclusion 

    This review demonstrated that integrating scRNA-seq-derived macrophage polarization biomarkers with next-generation mRNA and nanoparticle vaccine platforms offers a promising precision medicine strategy to counter MRSA immune evasion. These approaches may substantially reduce infection recurrence and complications in high-risk patients, paving the way for clinically effective vaccines in the era of antimicrobial resistance.

    Citation: Rouzbeh Sojoudi Masuleh, Fatemeh Roozbahani, Mohammad Hossein Rezapour, Zahra sharifi, Sarina Toorajmehr, Maedeh yousefi, Ghazal Hormozi, Mohammad Karimbakhsh. Clinical efficacies of immune-cell-targeted interventions a revolutionary era in host immune gene expression in MRSA infections[J]. AIMS Allergy and Immunology, 2026, 10(2): 116-130. doi: 10.3934/Allergy.2026010

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  • Background and aims 

    Methicillin-resistant Staphylococcus aureus (MRSA) remains a major cause of healthcare-associated infections worldwide, frequently progressing to bacteremia, and with high mortality rates, particularly in patients with recurrent or persistent infections involving skin/soft tissue and the bloodstream. Traditional antibiotic therapies are increasingly limited by MDR and immune evasion mechanisms. This review synthesized host immune transcriptomic changes during MRSA infections and evaluated the clinical translational potential of next-generation vaccines developed after 2020.

    Methods 

    Relevant searches were conducted in PubMed, Embase, and Web of Science (2020–2025) using combinations of terms related to MRSA, host immune gene expression, transcriptomics, scRNA-seq, and next-generation vaccines. Eligible studies included original research and reviews reporting primary data on immune transcriptomics or vaccine immunogenicity/protective efficacy in MRSA infections.

    Results 

    MRSA infection triggers strong innate immune activation (TLR2/NOD2 signaling, IL-1β/IL-6/TNF-α upregulation) and heterogeneous macrophage polarization (M1 proinflammatory vs. M2 immunosuppressive phenotypes), alongside adaptive Th1/Th17 responses that are undermined by superantigens, IL-10 hypersecretion, and PD-1-mediated exhaustion. Multivalent mRNA-LNP vaccines encoding ClfA-Hla-IsdB fusions induce strong Th1/Th17 immunity, ~80% opsonophagocytic killing activity, 90% reduction in bacterial load, and 75% survival in murine sepsis models.

    Conclusion 

    This review demonstrated that integrating scRNA-seq-derived macrophage polarization biomarkers with next-generation mRNA and nanoparticle vaccine platforms offers a promising precision medicine strategy to counter MRSA immune evasion. These approaches may substantially reduce infection recurrence and complications in high-risk patients, paving the way for clinically effective vaccines in the era of antimicrobial resistance.



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    Conflict of interest


    The authors have no conflicts of interest to declare.

    Author contributions


    Conceptualization: Mohammad Karimbakhsh, Rouzbeh Sojoudi Masuleh, Fatemeh Roozbahani; Data curation: All authors; Formal analysis: Mohammad Karimbakhsh, Rouzbeh Sojoudi Masuleh, Maedeh Yousefi; Investigation: All authors; Methodology: Mohammad Karimbakhsh, Rouzbeh Sojoudi Masuleh, Fatemeh Roozbahani; Project administration: Mohammad Karimbakhsh, Fatemeh Roozbahani; Resources: Mohammad Karimbakhsh, Rouzbeh Sojoudi Masuleh, Zahra sharifi; Validation: Mohammad Karimbakhsh, Rouzbeh Sojoudi Masuleh; Visualization: Mohammad Karimbakhsh, Fatemeh Roozbahani; Writing–original draft: All authors; Writing–reviewing & editing: All authors.

    Ethics approval of research


    Ethical approval was not required for this study because it is a review article based exclusively on previously published literature and did not involve human participants, animals, patient data, or clinical specimens.

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