Question

Mycobacterium tuberculosis and Listeria monocytogenes are both facultative intracellular parasites in humans. These pathogens have the ability to grow and multiply inside phagocytes. Artificial passive immunity against these infections can be achieved only by transferring E rosette forming leukocytes along with their corresponding adherent cells from an immune individual. E-rosette forming cells alone are incapable of effecting this transfer. Transferring E rosette forming leukocytes along with their corresponding adherent cells from a tuberculin skin positive individual will confer passive immunity to an individual undergoing a mixed lung infection caused by Mycobacterium tuberculosis and Listeria monocytogenes. However, such transfer will not confer immunity to an individual who is infected only with Listeria monocytogenes. Explain the nature of this immunologic discrepancy.

Answer 1

L. monocytogenes produce an important virulence factor LLO (Listeriolysin O) which has demonstrated role in inhibition and killing of leukocytes. Also, it is well known that IFN-gamma is extremely important for clearing of Listeria infection as it has been shown that IFN-gamma null mice fail to clear the infection.

On the other hand M. tuberculosis infection is a potent source of IFN-gamma production by Natural Killer cells via TNF alpha and IL-12 mediation. Therefore, E rosettes when passively transferred into only Listeria infected patients are partly destroyed by LLO virulence factor of Listeria and also they do not find heightened level of IFN-gamma in their micro-environment; however a patient co-infected with M. tuberculosis and L. monocytogenes has very high level of IFN-gamma and activated NK cells which in turn activate E rosette leukocytes and other macrophages to become bactericidal, thereby clearing Listeria and Mycobacterium infection.

This is a classic example of synergy between adaptive and innate immune response.