Helminth Coinfection Alters Monocyte Activation, Polarization, and Function in Latent Mycobacterium tuberculosis Infection.

Helminth infections are known to influence T and B cell responses in latent tuberculosis infection (LTBI). Whether helminth infections also modulate monocyte responses in helminth-LTBI coinfection has not been fully explored. To this end, we examined the activation, polarization, and function of human monocytes isolated from individuals with LTBI with (n = 25) or without (n = 25) coincident Strongyloides stercoralis infection (S. stercoralis-positive and S. stercoralis-negative respectively). Our data reveal that the presence of S. stercoralis infection is associated with lower frequencies of monocytes expressing CD54, CD80, CD86 at baseline (absence of stimulation) and in response to mycobacterial-Ag stimulation than monocytes from S. stercoralis-negative individuals. In contrast, S. stercoralis infection was associated with higher frequencies of M2-like monocytes, as determined by expression of CD206 and CD163. Monocytes from S. stercoralis-positive individuals had a reduced capacity to phagocytose or exhibit respiratory burst activity following mycobacterial-Ag or LPS stimulation and were less capable of expression of IL-1ß, TNF-α, IL-6, and IL-12 at baseline and/or following Ag stimulation compared with those without S. stercoralis infection. In addition, definitive treatment of S. stercoralis infection resulted in a significant reversal of the altered monocyte function 6 mo after anthelmintic therapy. Finally, T cells from S. stercoralis-positive individuals exhibited significantly lower activation at baseline or following mycobacterial-Ag stimulation. Therefore, our data highlight the induction of dampened monocyte activation, enhanced M2 polarization, and impaired monocyte function in helminth-LTBI coinfection. Our data also reveal a different mechanism by which helminth infection modulates immune function in LTBI.

Parasitic infection may be associated with discordant responses to QuantiFERON and tuberculin skin test in apparently healthy children and adolescents in a tuberculosis endemic setting, Ethiopia.

BACKGROUND: M. tuberculosis remains one of the world's deadliest pathogens in part because of its ability to establish persistent, latent infections, which can later reactivate to cause disease. In regions of the globe where disease is endemic, as much as 50% of the population is thought to be latently infected, complicating diagnosis and tuberculosis control. The tools most commonly used for diagnosis of latent M. tuberculosis infection are the tuberculin skin test and the newer interferon-gamma release assays, both of which rely on an antigen-specific memory response as an indicator of infection. It is clear that the two tests, do not always give concordant results, but the factors leading to this are only partially understood. METHODS: In this study we examined 245 healthy school children aged from 12 to 20 years from Addis Ababa, a tuberculosis-endemic region, characterised them with regard to response in the tuberculin skin test and QuantIFERON™ test and assessed factors that might contribute to discordant responses. RESULTS: Although concordance between the tests was generally fair (90% concordance), there was a subset of children who had a positive QuantIFERON™ result but a negative tuberculin skin test. After analysis of multiple parameters the data suggest that discordance was most strongly associated with the presence of parasites in the stool. CONCLUSIONS: Parasitic gut infections are frequent in most regions where M. tuberculosis is endemic. This study, while preliminary, suggests that the tuberculin skin test should be interpreted with caution where this may be the case.

Modulation of mycobacterial-specific Th1 and Th17 cells in latent tuberculosis by coincident hookworm infection.

Hookworm infections and tuberculosis (TB) are coendemic in many parts of the world. It has been suggested that infection with helminth parasites could suppress the predominant Th1 (IFN-γ-mediated) response needed to control Mycobacterium tuberculosis infection and enhance susceptibility to infection and/or disease. To determine the role of coincident hookworm infection on responses at steady-state and on M. tuberculosis-specific immune responses in latent TB (LTB), we examined the cellular responses in individuals with LTB with or without concomitant hookworm infection. By analyzing the expression of Th1, Th2, and Th17 subsets of CD4(+) T cells, we were able to demonstrate that the presence of coincident hookworm infection significantly diminished both spontaneously expressed and M. tuberculosis-specific mono- and dual-functional Th1 and Th17 cells. Hookworm infection, in contrast, was associated with expanded frequencies of mono- and dual-functional Th2 cells at both steady-state and upon Ag stimulation. This differential induction of CD4(+) T cell subsets was abrogated upon mitogen stimulation. Additionally, coincident hookworm infection was associated with increased adaptive T regulatory cells but not natural regulatory T cells in LTB. Finally, the CD4(+) T cell cytokine expression pattern was also associated with alterations in the systemic levels of Th1 and Th2 cytokines. Thus, coincident hookworm infection exerts a profound inhibitory effect on protective Th1 and Th17 responses in LTB and may predispose toward the development of active tuberculosis in humans.