Modulation of Protective and Pathological Immunity in Mycobacterial Infections

Abstract

Mycobacterial infections represent major problems to global health care. Tuberculosis is feared particularly because of its high mortality rates whereas in leprosy the occurrence of immunopathology, particularly nerve damage, is a major problem since the bacillus itself is relatively harmless. Thus, both effective vaccination strategies as well as novel immunomodulating regimens are warranted for the control of morbidity and mortality in mycobacterial diseases. Since CD4⁺ Thl cells and type-1 cytokines play a key role both in protective immunity and immunopathology in mycobacterial infections, we here describe new pharmacological and cytokine-based strategies to regulate Th1 immunity.

Interleukin-10 promoter single-nucleotide polymorphisms as markers for disease susceptibility and disease severity in leprosy

“…7 Among the candidate genes involved in host-pathogen interactions, cytokines evidently play a critical role. 8 Interleukin-10 (IL-10) is a cytokine that seems to be involved in regulating protective immunity in leprosy. A higher tumor necrosis factor-a (TNF-a)/IL-10 ratio was correlated with a better prognosis in terms of clinical outcome of leprosy household contacts.…”

Central Memory CD4+ T Cells Are Responsible for the Recombinant Bacillus Calmette-Guérin ΔureC::hly Vaccine's Superior Protection Against Tuberculosis

“…The early appearance of T-helper 1 (Th1) type CD4 effector memory T cells (T EM ) secreting interferon γ (IFN-γ)/tumor necrosis factor α (TNF-α) has been considered crucial for orchestration of protective immunity in the infected lung, but recently, it has been questioned whether expression of these proinflammatory mediators in the lung is indeed sufficient for control of tuberculosis [11, 12]. Systemic maintenance of T M following vaccination and their recruitment to the lung following infection remains a key focus of vaccine and biomarker studies [13, 14]. …”

Vaccines

“…Thus, a Th2 response can be switched into a Th1 response in mice (Raz et al 1996;Ottenhoff et al 1997). These fundamentally different immune responses are now known to be modulated by T lymphocytes that secrete signalling molecules (cytokines) that either favour development of cellular immunity and discourage antibody immunity (known as T-helper type 1, or Th1 cells; or more broadly as the type 1 response) or secrete cytokines that favour antibody and discourage cellular immunity (T-helper type 2, Th2 or type 2 response).…”