Understanding Immune Responses to Viruses—Do Underlying Th1/Th2 Cell Biases Predict Outcome?
Abstract
:1. Introduction
2. Causes of Deviant Immune Response in Viral Infections
2.1. Heterosubtypic Immunity
2.2. Ageing
2.3. Ethnicity
2.4. Co-Morbidities
3. Strategies to Address the Deviant Response
3.1. Antivirals
3.2. Anti-Histamines
3.3. Adjuvants
3.4. Vitamin D
3.5. Dexamethasone
3.6. Patient Stratification
4. Discussion and Concluding Remarks
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Conflicts of Interest
References
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Feature | Virus | Effect on Host | Refs. |
---|---|---|---|
Host genetic susceptibility | |||
TNF-α (−308) GG genotype IL-10 (-592/-819/-1082) CCA/ATA genotype IL-10 (-592/-819/-1082) ATA/ATG genotype | Dengue | Development of severe dengue in Sri Lankan patients. Risk factor to developing DHF. Protective factor from DHF. | [16] |
G6PD gene | Dengue, coronavirus, enterovirus | Deficiency enhances viral infection. | [17,18,19] |
A117V polymorphism in the NS2A | Zika | Increased virulence by reducing host innate immune responses and viral-induced apoptosis in vitro. | [20] |
HLA DRB1*11 | HCV | Protects from disease progression. | [21] |
HLA*0405, HLA DRB1*0301, DQB1*0201 | HCV | Viral persistence and chronic infection. | [22] |
IFIH1 | RSV | Deficient individuals unable to induce IFN-β, rendering them susceptible to infection. | [23] |
Q421X | IAV | Impaired IFN-α production causes life-threatening condition. | [24] |
Ageing | |||
Axl, Mertk | WNV | Age-related upregulation of regulatory receptors facilitates viral uptake by increasing blood–brain barrier permeability. | [25] |
T-cell defects | WNV | Insufficient number and quality of effector antiviral T-cells underlie age-related susceptibility to WNV. | [26] |
Histone modifications | IAV | Age-associated altered histone expression decreases IFN production by myeloid DCs. | [27] |
miR-181a deficiency in T-cells | WNV | Hallmark of ageing. Impairs T-cell expansion, viral clearance, and recall response. | [28] |
Ethnicity | |||
IFN | HCV | IFN effectiveness in blocking viral production significantly greater in White versus African-American patients. | [29] |
ACE2 | COVID-19 | ACE2 (receptor for cellular entry) expression significantly higher among Asians compared to African-Americans and Caucasians. | [30] |
Nab | Rubella | Individuals of African descent have significantly higher rubella-specific NAb levels than European or Hispanic individuals. | [31] |
Co-morbidities | |||
Obesity | Influenza H1N1 | Decreased CD8+ T-cell activation results in inability to mount protective immune response | [32] |
Asthma | IAV | Increased susceptibility to heterologous secondary influenza due to defective mucosal antibody responses. | [33] |
Cancer (melanoma/RCC) | Tumour antigen-specific Th2-type polarisation of CD4+ T-cell responses in the peripheral blood of patients with RCC or melanoma. | [34] | |
Type 2 airway disorders (allergic asthma, allergic rhinitis, CRSwNP) | HRV16 | Type 2 cytokines increase susceptibility to viral infection in airways via changing the epithelial structure and production of interferons. A Th2 bias induces a deficit in defending the mucosa against viral and bacterial infections. | [35] |
Evidence for Th Polarisation | Ref. | |
---|---|---|
Th1 | ||
Atherosclerosis | CD4+ T-cells dominate atherosclerotic plaques. Increase IFN-γ and IL-2, IL-12, IL-18. | [70] |
Rheumatoid arthritis | Increase in IFN-γ+CD4+ T-cells in peripheral blood and IFN-γ and TNF-α expression. Reduction in IL-6 and IL10 expression. | [105] |
Type I diabetes | High IFN-γ expression drives persistent signal in pancreatic beta cells. | [106] |
Multiple sclerosis | IFN-γ-producing Th1 cells most frequent Th cell subset in the CNS. | [107] |
Parkinson’s | PD patients more Th1 cells and fewer Treg cells. CD4+ T-cells mediate brain inflammation. | [108] [109] |
Th2 | ||
Asthma | Production of Th2 cytokines IL-4, IL-13, IL-5, increased production of IgE by B-cells. Genes that enhanced Th2 polarisation (IL17RB) and Th2 cytokine (IL-25) production were upregulated in asthma. | [110] [111] |
Ulcerative colitis | Overexpression of Bcl2L12 by CD4+ T-cells upregulates Th2 responses and downregulates Th2 ell apoptosis. | [112] |
Chronic fatigue syndrome | Shift from Th1 to Th2 profile correlated with illness parameters including increase in IL-4 and reduced natural killer cell cytotoxicity. | [113] |
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Howard, F.H.N.; Kwan, A.; Winder, N.; Mughal, A.; Collado-Rojas, C.; Muthana, M. Understanding Immune Responses to Viruses—Do Underlying Th1/Th2 Cell Biases Predict Outcome? Viruses 2022, 14, 1493. https://doi.org/10.3390/v14071493
Howard FHN, Kwan A, Winder N, Mughal A, Collado-Rojas C, Muthana M. Understanding Immune Responses to Viruses—Do Underlying Th1/Th2 Cell Biases Predict Outcome? Viruses. 2022; 14(7):1493. https://doi.org/10.3390/v14071493
Chicago/Turabian StyleHoward, Faith H. N., Amy Kwan, Natalie Winder, Amina Mughal, Cristal Collado-Rojas, and Munitta Muthana. 2022. "Understanding Immune Responses to Viruses—Do Underlying Th1/Th2 Cell Biases Predict Outcome?" Viruses 14, no. 7: 1493. https://doi.org/10.3390/v14071493