Mycobacterium tuberculosis GroEL2 Modulates Dendritic Cell Responses

• Authors: Maria Georgieva, Emory University; Jonathan Kevin Sia, Emory University; Erica Bizzell, Emory University; Ranjna Madan Lala, Emory University; Jyothi Rengarajan, Emory University
• Journal Title: Infection and Immunity
• Volume: Volume 86, Number 2
• Publisher: American Society for Microbiology | 2018-02-01, Pages e00387-17
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1128/IAI.00387-17
• Subjects: Health Sciences, Immunology
• Keywords: Science & Technology; Life Sciences & Biomedicine; Immunology; Infectious Diseases; Mycobacterium tuberculosis; dendritic cells; IMMUNE-RESPONSE; IN-VIVO; PROTEINS; CPN60.2; SURFACE; HSP65; MICE; ASSOCIATION; MACROPHAGES; ACTIVATION

Abstract

Mycobacterium tuberculosis successfully subverts the host immune response to promote disease progression. In addition to its known intracellular niche in macrophages, M. tuberculosis interferes with the functions of dendritic cells (DCs), which are the primary antigen-presenting cells of the immune system. We previously showed that M. tuberculosis dampens proinflammatory responses and impairs DC functions through the cell envelope-associated serine protease Hip1. Here we present data showing that M. tuberculosis GroEL2, a substrate of Hip1, modulates DC functions. The full-length GroEL2 protein elicited robust proinflammatory responses from DCs and promoted DC maturation and antigen presentation to T cells. In contrast, the cleaved form of GroEL2, which predominates in M. tuberculosis, was poorly immunostimulatory and was unable to promote DC maturation and antigen presentation. Moreover, DCs exposed to full-length, but not cleaved, GroEL2 induced strong antigen-specific gamma interferon (IFN-γ), interleukin-2 (IL-2), and IL-17A cytokine responses from CD4+T cells. Moreover, the expression of cleaved GroEL2 in the hip1 mutant restored the robust T cell responses to wild-type levels, suggesting that proteolytic cleavage of GroEL2 allows M. tuberculosis to prevent optimal DC-T cell cross talk during M. tuberculosis infection.