Abstract
The lungs are the most vulnerable site for air-borne infections. Immunologic compartmentalization of the lungs into airway lumen and interstitium has paved the way to determine the immune status of the site of pathogen entry, which is crucial for the outcome of any air-borne infections. Vaccination via the nasal route with Mycobacterium indicus pranii (MIP), a prospective candidate vaccine against tuberculosis (TB), has been reported to confer superior protection as compared to the subcutaneous (s.c.) route in small-animal models of TB. However, the immune mechanism remains only partly understood. Here, we showed that intranasal (i.n.) immunization of mice with MIP resulted in a significant recruitment of CD4+ and CD8+ T-cells expressing activation markers in the lung airway lumen. A strong memory T-cell response was observed in the lung airway lumen after i.n. MIP vaccination, compared with s.c. vaccination. The recruitment of these T-cells was regulated primarily by CXCR3–CXCL11 axis in “MIP i.n.” group. MIP-primed T-cells in the lung airway lumen effectively transferred protective immunity into naïve mice against Mycobacterium tuberculosis (M.tb) infection and helped reducing the pulmonary bacterial burden. These signatures of protective immune response were virtually absent or very low in unimmunized and subcutaneously immunized mice, respectively, before and after M.tb challenge. Our study provides mechanistic insights for MIP-elicited protective response against M.tb infection.
Highlights
Tuberculosis continues to be a major threat to human health worldwide
We found that i.n. vaccination with Mycobacterium indicus pranii (MIP) elicited strong CD4+ and CD8+ T-cell responses as well as robust T-helper 1 (Th1) recall response in lung airway lumen
Mycobacterium tuberculosis (H37Rv strain) and Mycobacterium indicus pranii (MIP) were grown in 7H9 media supplemented with 10% Albumin Dextrose Catalase (ADC), 0.2% glycerol and 0.05%/0.1% tween-80 for MIP/M.tb-H37Rv, respectively
Summary
The etiological agent, M.tb, has evolved in a manner to modulate the host immune response in its favor. Its complex cell-wall and secretome interferes with innate immune signaling pathways of the host, which culminates in a delayed onset of adaptive response at the primary site of infection. This delayed immune activation favors an exponential growth of M.tb and the successful establishment of infections [1]. Vaccine approach and the strategy of immunization play a crucial role in prevention against infectious diseases like TB. The whole bacterial vaccine approach has the advantage of multiple antigens and is built in adjuvanticity.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
