Abstract
BackgroundTh1 and Th17 responses are known to play an important role in immunity to pulmonary tuberculosis (PTB), although little is known about their role in extrapulmonary forms of tuberculosis (TB).MethodsTo identify the role of Th1, Th17, and Th22 cells in multi-focal TB lymphadenitis (TBL), we examined mycobacteria–specific immune responses in the whole blood of individuals with PTB (n = 20) and compared them with those with TBL (n = 25).ResultsElevated frequencies of CD4+ T cells expressing IFN- γ, TNF-α, and IL-2 were present in individuals with TBL compared with those with PTB at baseline and in response to ESAT-6 and CFP-10. Similarly, increased frequencies of CD4+ T cells expressing IL-17A, IL-17F, and IFN-γ were also present in individuals with TBL at baseline and following ESAT-6 and CFP-10 stimulation although no significant difference in frequency of Th22 cells was observed. Finally, frequencies of Th1 (but not Th17) cells exhibited a significantly negative correlation with natural regulatory T cell frequencies at baseline.ConclusionsMulti-focal TB lymphadenitis is therefore characterized by elevated frequencies of Th1 and Th17 cells, indicating that Th1 and Th17 responses in TB disease are probably correlates of disease severity rather than of protective immunity.
Highlights
Tuberculosis (TB) is a spectral disease with host responses controlling disease severity and extrapulmonary dissemination
Multi-focal TB lymphadenitis is characterized by elevated frequencies of Th1 and Th17 cells, indicating that Th1 and Th17 responses in TB disease are probably correlates of disease severity rather than of protective immunity
We show that frequencies of natural Tregs in individuals with TB disease were inversely related to frequencies of mono- and multifunctional Th1 but not Th17 cells
Summary
Tuberculosis (TB) is a spectral disease with host responses controlling disease severity and extrapulmonary dissemination. How Mtb-infected individuals become more susceptible to extrapulmonary dissemination following initial infection is not known. Extrapulmonary TB is a significant health problem worldwide because of the difficulties of diagnosis and treatment. Tuberculous lymphadenitis (TBL) is the most common presentation of extrapulmonary TB, accounting for 30–40% of cases [2]. Multi-focal TBL is thought to reflect extrapulmonary spread by the hematogenous route from an initial focus in the lung and, as such, represents a more disseminated form of active TB disease [3]. Th1 and Th17 responses are known to play an important role in immunity to pulmonary tuberculosis (PTB), little is known about their role in extrapulmonary forms of tuberculosis (TB)
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