Abstract
Lack of understanding of the immune response to mycobacterial pathogens has impeded progress in development of vaccines. Infection leads to development of an immune response that controls infection but is unable to eliminate the pathogen, resulting in a persistent infection. Although this puzzle remains to be solved, progress has been made using cattle as a model species to study the immune response to a prototypic mycobacterium, Mycobacterium a. paratuberculosis (Map). As chronicled in the review, incremental advances in characterizing the immune response to mycobacteria during the last 30 years with increases in information on the evolution of mycobacteria and relA, a gene regulating the stringent response, have brought us closer to an answer. We provide a brief overview of how mycobacterial pathogens were introduced into cattle during the transition of humankind to nomadic pastoralists who domesticated animals for food and farming. We summarize what is known about speciation of mycobacteria since the discovery of Mybacterium tuberculsis Mtb, M. bovis Mbv, and Map as zoonotic pathogens and discuss the challenges inherent in the development of vaccines to mycobacteria. We then describe how cattle were used to characterize the immune response to a prototypic mycobacterial pathogen and development of novel candidate vaccines.
Highlights
Introduction iationsComparative phylogenomic studies show that Mycobacterium tuberculosis (Mtb), M.bovis (Mbv), and M. avium subsp. paratuberculosis (Map) are members of a lineage of bacteria that emerged well before the dawn of civilization [1,2]
The studies had not demonstrated whether the cells proliferating in response to stimulation with antigen-presenting cells (APC) pulsed with Mycobacterium a. paratuberculosis (Map)/relA or MMP had any direct effect on the viability of bacteria present in macrophages used as targets
The development of the bovine model has introduced a platform where information on the immune response to mycobacteria and candidate vaccines obtained from studies in mice, humans, non-human primates, and cattle can be compared
Summary
Johne’s Disease’ was to determine whether there is an age-related difference in susceptibility to infection with Map. Tritiated thymidine incorporation was still used as the primary method of analysis of the proliferative response to antigen (Ag) stimulation ex vivo in tissue culture [23]. Flow cytometry was introduced as a method to characterize the phenotype of cells present in cultures of PBMC stimulated with PPD or sonicates of Map (SAg) [24]. Analysis revealed all animals were infected when exposed under experimental conditions and developed an antibody response and a cell-mediated response. Analysis of the recall response revealed there was a proliferative response to stimulation with PPD and soluble antigens (Sags) of Map. Analysis of the phenotype of cells proliferating in response to Ag stimulation revealed memory CD45R0+ CD4 T cells were the major component of this population [23]. A follow-up study yielded similar results and revealed that memory CD45R0+ CD8 T cells were detected, but CD4 T cells were dominant in all cultures [24]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
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 call
