A Ferritin Mutant Induces Protective Immunity against Virulent Mycobacterium tuberculosis Infection

Iron plays a critical role in the pathogenesis of many organisms including Mtb. It is the preferred redox cofactor in many basic cellular processes but due to its insolubility and potential toxicity under physiological conditions is a limiting nutrient in the host environment. Previously, we demonstrated that Mtb requires the iron storage protein ferritin (BfrB), for adaptation to both low and sufficient concentrations of environmental iron. We also showed that absence of bfrB compromises the ability of Mtb to overcome iron deficiency and prevent excess iron toxicity. In this study, we tested whether vaccination with bfrB could elicit host protective immune response against virulent Mtb infection. The results show that immunization of mice with the bfrB stimulates protective immunity associated with reduced immunopathology and better containment of the infection compared to vaccination with BCG. Genome-wide transcriptome analysis showed a distinct expression pattern of significantly differentially expressed genes (SDEG) between the bfrB and BCG-vaccinated, Mtb-infected mice lungs. Our network/pathway analysis of SDEG revealed significant inhibition of inflammatory response genes and activation of fibrosis genes in the bfrB, compared to BCG vaccinated, Mtb-infected mice lungs. The results provide a frame work for the study of mechanisms of protection relevant for the design of new and improved preventive strategies for TB.

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