Local Immune Responses Correlate with Presentation and Outcome in Tuberculosis

Abstract

Local cellular immune responses may affect presentation and outcome in tuberculosis (TB). To investigate this hypothesis, we performed bronchoalveolar lavage (BAL) on 30 patients with untreated pulmonary tuberculosis and assessed the type of cellular inflammatory response and cytokine production. We then correlated BAL findings and cytokine production with clinical findings. We also performed BAL on a subset of patients to examine changes in cytokine production by BAL cells over time. We found that at presentation patients with less clinically and radiographically advanced TB (smear-negative, noncavitary disease) had a local immune response characterized by a predominance of lymphocytes. Furthermore, BAL cells from these patients secreted interferon (IFNgamma), and not Interleukin-4, suggesting a Th 1-type lymphocytic response. In patients with smear-positive and/or cavitary disease, macrophages or polymorphonuclear leukocytes were the predominant BAL cell type, but with treatment and clinical improvement these patients went on to recruit IFNgamma producing cells to the lung. We conclude that the type of cellular immune response that occurs locally in the lung may affect presentation and outcome in pulmonary TB, and an understanding of the development of this response may lead to insights into pathogenesis and novel therapies for TB.

A Model to Predict Cell-Mediated Immune Regulatory Mechanisms During Human Infection withMycobacterium tuberculosis

“…7, compare A with B). T lymphocyte-macrophage ratios and absolute cell counts for this and other activation scenarios generated by our model also correspond well with human clinical observations (67,68,70).…”

“…6A presents the corresponding macrophage results for latency. Resting macrophages in the absence of infection maintain an equilibrium near 3 ϫ 10 5 cells/ml (67)(68)(69)(70). Despite their continual recruitment, the drop in resting macrophages during infection indicates a gain (transfer) to either the activated or infected cell classes.…”

Pleural fluid from tuberculous pleurisy inhibits the functions of T cells and the differentiation of Th1 cells via immunosuppressive factors

“…Th1 cytokines were associated with protective immunity against Mtb. [15][16][17] Despite the heightened levels of inflammatory mediators, several immune factors that lead to suppression of T-cell functions have been identified in current research. 18,19 Thus, the balance between pro-and anti-inflammatory mediators seems to be crucial to the final outcome of tuberculosis.…”

Spontaneous or Mycobacterium tuberculosis‐induced apoptotic neutrophils exert opposite effects on the dendritic cell‐mediated immune response

“…Polymorphonuclear neutrophils (PMN) are key players of the innate immune system providing a first line of defense against pathogens [11]. In particular, circulating PMN from patients with tuberculosis become activated, and being recruited to the lungs early in infection, they are activated by Mtb, inducing the production of several pro-inflammatory cytokines and chemokines [12,13].…”