Active tuberculosis in Africa is associated with reduced Th1 and increased Th2 activity in vivo

Abstract

Activation of Th1 lymphocytes, IFN‐γ production and macrophage activation are crucial in defense against Mycobacteria. In developing countries, Th2 activation and IL‐4 production have been associated in vitro with tuberculosis and with poor clinical outcome after treatment. Serological markers of Th1 [soluble lymphocyte activation gene (LAG)‐3] and Th2 (IgE, solubleCD30, and CCL22/macrophage‐derived chemokine) activity were measured in 414 HIV‐negative tuberculosis patients from The Gambia and Guinée and in 414 healthy household and community controls. Measurements were repeated during treatment to assess the effect of therapy on Th1/Th2 ratio. At diagnosis, sLAG‐3 levels were lower in patients than in community controls (p<0.0001), but were higher in household controls exposed to contact with patients than in community controls (p<0.0001). In comparison with community controls, patients had consistently higher levels of IgE, sCD30, and CCL22 (p<0.0001), whereas household controls had lower levels of indicators of Th2 activity (p<0.0001). After treatment, cured patients had higher levels of Th1 (p<0.0001) and lower levels of Th2 (p<0.0001) activity than patients who were not successfully treated or interrupted therapy. In Africa, tuberculosis is associated with low Th1 and high Th2 activity in vivo, whereas close exposure to tuberculosis is associated with a high Th1/Th2 ratio. Patients with favorable outcome after treatment exhibit a higher Th1/Th2 ratio compared to patients with poor clinical outcome.

Alternative activation deprives macrophages of a coordinated defense program to Mycobacterium tuberculosis

“…The signals that trigger resuscitation of the pathogen prior to reactivation are largely unknown, and it is currently debated whether reactivation is promoted by a shift from type 1 to type 2 cytokines [6], consistent with the observation that the latter cytokines inhibit in vitro production of IFN-c [7]. Several studies have demonstrated that human tuberculosis is paralleled by an increased Th2 response comprising the cytokines IL-4 and IL-13 [8][9][10][11][12], as well as IL-4-dependent IgE secretion [13]. Evidence for Th2 cytokines in murine tuberculosis includes the findings that mycobacterial lipids induce IL-4 production by bone marrow cells [14] and that generation of IgG1 antibody to cardiolipin depends on IL-4 [15].…”

Cytokine profile during latent and slowly progressive primary tuberculosis: a possible role for interleukin-15 in mediating clinical disease

“…Our results confirm (in mice) earlier reports that IL-4 is generated in the lungs of human TB patients [37][38][39][40]. On the other hand, however, we observed neither an increase in IL-4 expression with disease progression nor the downregulation of Th1 cytokines, associated with this cytokine, reported by Biedermann et al [41].…”

Ramp-ing up allergies: Nramp1 (Slc11a1), macrophages and the hygiene hypothesis

“…These T helper 2 (Th2) cytokines also have a protective role during helminth infections but cause susceptibility to bacterial infections like tuberculosis [47]. A geneticand environmental-based balance in Th1/Th2 cytokines could affect the development of infectious and allergic disease.…”