Nutritional immunity is a major facet of host defense, wherein the host immune system strategically limits pathogen access to critical nutrients, including iron, zinc, vitamins, lipids, and amino acids, to repress microbial proliferation and virulence. This review provides a comprehensive synthesis of the molecular mechanisms that power nutrient immunity, including metal homeostasis, nutrient competition, transporter modulation, hormonal regulation, and direct antimicrobial actions. We examine nutrient-specific strategies employed by the host, such as iron-withholding mechanisms, vitamin deprivation, and copper-mediated toxicity. We also explore how diverse pathogens, including extracellular, intracellular, and eukaryotic pathogens, adapt to these hostile nutritional landscapes through siderophore diversification, regulatory integration, and metabolic rewiring. Comparative genomic analyses reveal convergent evolution in nutrient acquisition systems, illuminating the dynamic arms race between host restriction and microbial evasion. We examine the immunological mechanisms that regulate nutritional immunity. Further, we discuss the translational potential of nutritional immunity, cutting across nutrient-based therapies, host-directed interventions, and emerging diagnostic biomarkers. Finally, we suggest future directions that synergize nutritional immunity with microbiome ecology, global malnutrition, and personalized medicine. By elucidating the interconnection between metabolism and immunity, this review highlights the therapeutic promise of starving or toxifying the pathogen to save the host.

Nutritional immunity is a major facet of host defense, wherein the host immune system strategically limits pathogen access to critical nutrients, including iron, zinc, vitamins, lipids, and amino acids, to repress microbial proliferation and virulence. This review provides a comprehensive synthesis of the molecular mechanisms that power nutrient immunity, including metal homeostasis, transporter modulation, hormonal regulation, and direct antimicrobial actions. We examine nutrient-specific strategies employed by the host, from iron withholding mechanisms to vitamin deprivation and copper-mediated toxicity. We also explore how diverse pathogens, including extracellular, intracellular, and eukaryotic, adapt to these hostile nutritional landscapes through siderophore diversification, regulatory integration, and metabolic rewiring. Comparative genomic analyses reveal convergent evolution in nutrient acquisition systems, illuminating the dynamic arms race between host restriction and microbial evasion. Further, we discuss the translational potential of nutritional immunity, cutting across nutrient-based therapies, host-directed interventions, and emerging diagnostic biomarkers. Finally, we suggest future directions that synergize nutritional immunity with microbiome ecology, global malnutrition, and personalized medicine. By elucidating the interconnection between metabolism and immunity, this review highlights the therapeutic promise of starving the pathogen to save the host.

Oncogenic viruses contribute to approximately 20% of human cancers globally, with their impact falling disproportionately on populations in Sub-Saharan Africa. In this region, cervical cancer, hepatocellular carcinoma, endemic Burkitt lymphoma, and Kaposi sarcoma represent major causes of cancer-related morbidity and mortality, driven by persistent infection with human papillomavirus (HPV), hepatitis B and C viruses (HBV/HCV), Epstein–Barr virus (EBV), Kaposi sarcoma-associated herpesvirus (KSHV), and human T-lymphotropic virus-1 (HTLV-1). This review synthesizes current insights into the immunological mechanisms that underpin viral carcinogenesis in Africa, emphasizing how defective viral clearance, chronic immune activation, and immune evasion arise from the convergence of region-specific co-infections, host genetic diversity, and environmental exposures. We examine the mechanistic roles of HIV-associated CD4⁺ T cell depletion, malaria-induced perturbation of antiviral T cell immunity, helminth-driven T helper 2 polarization, and tuberculosis-associated inflammatory signaling in promoting viral persistence and malignant transformation. In addition, the influence of the extensive diversity of African human leukocyte antigens (HLA) and cytokine gene polymorphisms on antiviral immune responses and cancer susceptibility was discussed. We also assessed how virus-associated tumors establish profoundly immunosuppressive microenvironments characterized by impaired antigen presentation and the dominance of immune checkpoint pathways. Finally, we examined how gaps in vaccination, screening, and diagnostic capacity intersect with immunological vulnerability across Africa, contributing to the burden of infection-associated cancers. These challenges position Africa as a critical setting for developing targeted, genotype-inclusive public health interventions and reducing global cancer disparities through advances in immunoprevention and immunotherapy.

Oncogenic viruses contribute to approximately 15–20% of human cancers globally, with their impact falling disproportionately on populations in Sub-Saharan Africa. In this region, cervical cancer, hepatocellular carcinoma, endemic Burkitt lymphoma, and Kaposi sarcoma represent major causes of cancer-related morbidity and mortality, driven by persistent infection with human papillomavirus (HPV), hepatitis B and C viruses (HBV/HCV), Epstein–Barr virus (EBV), Kaposi sarcoma–associated herpesvirus (KSHV), and human T-lymphotropic virus-1 (HTLV-1). This review synthesizes current insights into the immunological mechanisms that underpin viral carcinogenesis in Africa, emphasizing how defective viral clearance, chronic immune activation, and immune evasion arise from the convergence of region-specific co-infections, host genetic diversity, and environmental exposures. We examine the mechanistic roles of HIV-associated CD4⁺ T cell depletion, malaria-induced perturbation of antiviral T cell immunity, helminth-driven T helper 2 polarization, and tuberculosis-associated inflammatory signaling in promoting viral persistence and malignant transformation. In addition, the influence of the extensive diversity of African human leukocyte antigens (HLA) and cytokine gene polymorphisms on antiviral immune responses and cancer susceptibility was discussed. We also assessed how virus-associated tumors establish profoundly immunosuppressive microenvironments characterized by impaired antigen presentation and the dominance of immune checkpoint pathways. Finally, we examined how gaps in vaccination, screening, and diagnostic capacity intersect with immunological vulnerability across Africa, contributing to the burden of infection-associated cancers. These challenges position Africa as a critical setting for developing targeted, genotype-inclusive public health interventions and reducing global cancer disparities through advances in immunoprevention and immunotherapy.