Leveraging Antibody, B Cell and Fc Receptor Interactions to Understand Heterogeneous Immune Responses in Tuberculosis

Abstract

Despite over a century of research, Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), continues to kill 1.5 million people annually. Though less than 10% of infected individuals develop active disease, the specific host immune responses that lead to Mtb transmission and death, as well as those that are protective, are not yet fully defined. Recent immune correlative studies demonstrate that the spectrum of infection and disease is more heterogenous than has been classically defined. Moreover, emerging translational and animal model data attribute a diverse immune repertoire to TB outcomes. Thus, protective and detrimental immune responses to Mtb likely encompass a framework that is broader than T helper type 1 (Th1) immunity. Antibodies, Fc receptor interactions and B cells are underexplored host responses to Mtb. Poised at the interface of initial bacterial host interactions and in granulomatous lesions, antibodies and Fc receptors expressed on macrophages, neutrophils, dendritic cells, natural killer cells, T and B cells have the potential to influence local and systemic adaptive immune responses. Broadening the paradigm of protective immunity will offer new paths to improve diagnostics and vaccines to reduce the morbidity and mortality of TB.

B21 DNA vaccine expressing ag85b, rv2029c, and rv1738 confers a robust therapeutic effect against latent Mycobacterium tuberculosis infection

“…Using a mouse model, we examined the vaccine’s immunogenicity ( Figure 2A ). Protective antibodies may promote and increase the death of intracellular bacteria through FcR-mediated phagocytosis and improve immune responses through the rapid adsorption and processing of antigens ( 29 ). Therefore, we purified the fusion protein for the evaluation of serum antibody levels in mice after immunization ( Figure S2 ).…”

Antibody glycosylation correlates with disease progression in SIV‐Mycobacterium tuberculosis coinfected cynomolgus macaques

“…Our findings suggest impaired serum humoral responses against Mtb occur relatively early (< 6 months) following SIV infection. The SIV‐coinfected animals studied here had lower total CD4 + T‐cell counts at the time of Mtb coinfection, 16 and it is possible that the reduced T‐cell repertoire may impair the antibody response given the important roles of CD4 + T cells in providing B‐cell help 31 …”

“…The SIV-coinfected animals studied here had lower total CD4 + T-cell counts at the time of Mtb coinfection, 16 and it is possible that the reduced T-cell repertoire may impair the antibody response given the important roles of CD4 + T cells in providing B-cell help. 31 Our work was performed with a small cohort of 15 macaques (seven SIV-positive, eight SIV-na€ ıve), which may limit the strength of our conclusions. Whether these observations apply to human cohorts remains to be confirmed.…”

Microbiome Alteration in Lung Tissues of Tuberculosis Patients Revealed by Metagenomic Next-Generation Sequencing and Immune-Related Transcriptional Profile Identified by Transcriptome Sequencing

“…26 Our KEGG analysis data showed that NF-κB, B cell receptor, Fc epsilon RI, and Toll-like receptor signaling pathways were enriched in the TB group compared with NonTB or ParaTB groups. Thereinto, the NF-κB signaling pathway is up-regulated considerably in active TB patients and regulates immune response, 9 B cells modulate IL-10 and inflammation during Mtb infection, 27 Fc receptors on immune cells can influence TB's local and systemic adaptive immune responses, 28 and Toll-like receptors are the essential pattern recognition receptors detecting Mtb in the first step of initiation. 25 These signaling pathways are substantially involved in the early immune reaction of encountering Mtb.…”