Intramuscular Boosting with hIFN-Alpha 2b Enhances BCGphipps-Induced Protection in a Murine Model of Leprosy

Gloria G Guerrero,Javier Rangel-Moreno,Oscar Rojas-Espinosa,Sergio O Islas-Trujillo

doi:10.3390/microbiolres12030051

Abstract

Host immunity to Mycobacterium leprae encompasses a spectrum of mechanisms that range from cellular immunity-driven protection to damage associated with humoral immunity as in type-2 leprosy reactions. Although type I interferons (IFNs) participate in eliminating intracellular pathogens, their contribution to the production of antibodies and CD3+ FOXP3+ regulatory T cells (Tregs) in BCG vaccine-mediated protection in leprosy is unknown. BCGphipps (BCGph) priming followed by intramuscular hIFN-α 2b boost significantly reduced lesion size and Mycobacterium lepraemurium growth in the skin. T follicular regulatory cells (TFR), a subset of Tregs induced by immunization or infection, reside in the germinal centers (GCs) and modulate antibody production. We found impaired Treg induction and improved GCs in draining lymph nodes of BCGph primed and hIFN-α 2b boosted mice. Moreover, these mice elicited significant amounts of IL-4 and IL-10 in serum. Thus, our results support the adjuvant properties of hIFN-α 2b in the context of BCGph priming to enhance protective immunity against skin leprosy.

Highlights

Mycobacterium leprae and Mycobacterium lepromatosis, the etiological agents of human leprosy [1,2], affect the skin and peripheral nerves [3]
After blindly counting CD3+ FOXP3+ Tregs in the Draining Lymph Nodes (DLNs) of our experimental mice, we found that Tregs were significantly reduced in the DLNs of mice after BCGph priming (p = 0.0013), hIFN-α 2b inoculation (p = 0.0074), or combined BCGph priming and hIFN-α 2b boosting (p = 0.0013) as compared with mice challenged with Mycobacterium lepraemurium (MLM)
Consistent with our observations, we found a significant reduction in the average germinal centers (GCs) size in the DLNs after hIFN-α 2b injection and in the BCGph priming/hIFN-α 2b boosting protocol (Figure 5E)

Summary

Introduction

Mycobacterium leprae and Mycobacterium lepromatosis, the etiological agents of human leprosy [1,2], affect the skin and peripheral nerves [3]. Multidrug treatments (MDT) for leprosy are available, the number of new cases remains stable (700,000 per year). The lack of an effective diagnostic procedure makes tracking of M. leprae transmission difficult [4,5,6,7]. The spectrum of clinical manifestations in leprosy correlates with the type of immune response elicited. Tuberculoid leprosy (TT), characterized by a dominant Th1 response, restricts bacilli growth via IFN-γdriven activation of microbicidal functions of macrophages. The production of classic Th2 cytokines (IL-4 and IL-10) has been associated with loss of protection and enhanced bacillary growth in disseminated lepromatous leprosy (LL) [10]. There are intermediate subtypes that represent a mixture of Th1 and Th2 responses [10]

Methods

Results

Discussion

Conclusion