The role of neutrophils in tuberculosis (TB) resistance and pathology is poorly understood. Neutrophil reactions are meant to target the offending pathogen but may lead to destruction of the host lung tissue, making the defending cells an enemy. Here, we show that mice of the I/St strain which are genetically susceptible to TB show an unusually high and prolonged neutrophil accumulation in their lungs after intratracheal infection. Compared to neutrophils from more resistant A/Sn mice, I/St neutrophils display an increased mobility and tissue influx, prolonged lifespan, low expression of the CD95 (Fas) apoptotic receptor, relative resistance to apoptosis, and an increased phagocytic capacity for mycobacteria. Segregation genetic analysis in (I/St ؋ A/Sn)F 2 hybrids indicates that the alleles of I/St origin at the chromosome 3 and 17 quantitative trait loci which are involved in the control of TB severity also determine a high level of neutrophil influx. These features, along with the poor ability of neutrophils to restrict mycobacterial growth compared to that of lung macrophages, indicate that the prevalence of neutrophils in TB inflammation contributes to the development of pathology, rather than protection of the host, and that neutrophils may play the role of a "Trojan horse" for mycobacteria.

The outcome of Mycobacterium tuberculosis (Mtb) infection ranges from a complete pathogen clearance through asymptomatic latent infection (LTBI) to active tuberculosis (TB) disease. It is now understood that LTBI and active TB represent a continuous spectrum of states with different degrees of pathogen “activity,” host pathology, and immune reactivity. Therefore, it is important to differentiate LTBI and active TB and identify active TB stages. CD4+ T cells play critical role during Mtb infection by mediating protection, contributing to inflammation, and regulating immune response. Th1 and Th17 cells are the main effector CD4+ T cells during TB. Th1 cells have been shown to contribute to TB protection by secreting IFN-γ and activating antimycobacterial action in macrophages. Th17 induce neutrophilic inflammation, mediate tissue damage, and thus have been implicated in TB pathology. In recent years new findings have accumulated that alter our view on the role of Th1 and Th17 cells during Mtb infection. This review discusses these new results and how they can be implemented for TB diagnosis and monitoring.

Tuberculosis disease (TB) may progress at different rates and have different outcomes. Neutrophils have been implicated in TB progression; however, data on their role during TB are controversial. Here we show that in mice, TB progression is associated with the accumulation of cells that express neutrophilic markers Gr-1 and Ly-6G, but do not belong to conventional neutrophils. The cells exhibit unsegmented nuclei, have Gr-1dimLy-6GdimCD11b+ phenotype and express F4/80, CD49d, Ly-6C, CD117, CD135 markers characteristic not of neutrophils, but of immature myeloid cells. The cells accumulate in the lungs, bone marrow, spleen and blood at the advanced (pre-lethal) stage of M. tuberculosis infection and represent a heterogeneous population of myeloid cells at different stages of their differentiation. The accumulation of Gr-1dimCD11b+ cells is accompanied by the disappearance of conventional neutrophils (Gr-1hiLy-6Ghi-expressing cells). The Gr-1dimCD11b+ cells suppress T cell proliferation and IFN-γ production in vitro via NO-dependent mechanisms, i.e. they exhibit characteristics of myeloid-derived suppressor cells (MDSCs). These results document the generation of MDSCs during TB, suggesting their role in TB pathogenesis, and arguing that neutrophils do not contribute to TB pathology at the advanced disease stage.

Infection with M. tuberculosis remains one of the most common infections in the world. The outcome of the infection depends on host ability to mount effective protection and balance inflammatory responses. Neutrophils are innate immune cells implicated in both processes. Accordingly, during M. tuberculosis infection, they play a dual role. Particularly, they contribute to the generation of effector T cells, participate in the formation of granuloma, and are directly involved in tissue necrosis, destruction, and infection dissemination. Neutrophils have a high bactericidal potential. However, data on their ability to eliminate M. tuberculosis are controversial, and the results of neutrophil depletion experiments are not uniform. Thus, the overall roles of neutrophils during M. tuberculosis infection and factors that determine these roles are not fully understood. This review analyzes data on neutrophil defensive and pathological functions during tuberculosis and considers hypotheses explaining the dualism of neutrophils during M. tuberculosis infection and tuberculosis disease.

Genetic control of susceptibility to tuberculosis (TB) is being intensively studied, and immune responses to mycobacteria are considerably well characterized. However, it remains largely unknown which parameters of response distinguish resistant and susceptible TB phenotypes. Mice of I/St and A/Sn inbred strains and (A/Sn × I/St)F1 hybrids were previously categorized as, respectively, susceptible, resistant, and hyperresistant to Mycobacterium tuberculosis-triggered disease. In the present work we compared parameters of lung T cell activation and response following M. tuberculosis challenge. In all mice, the disease progression was accompanied by a marked accumulation in the lungs of activated CD4+ (CD44high/CD45RBlow) and CD8+ (CD44high/CD45RB+) T cells capable of secreting IFN-γ and of activating macrophages for NO production and mycobacterial growth inhibition. However, significantly more CD8+ T cells were accumulated in the lungs of resistant A/Sn and F1 compared with I/St mice. About 80% A/Sn and F1 CD8+ cells expressed CD44high/CD45RB+ phenotype, while about 40% I/St CD8+ cells did not express CD45RB marker at week 5 of infection. In contrast, in susceptible I/St mice lung CD4+ cells proliferated much more strongly in response to mycobacterial sonicate, and a higher proportion of these cells expressed CD95 and underwent apoptosis compared with A/Sn cells. Unseparated lung cells and T cells of I/St origin produced more IL-5 and IL-10, respectively, whereas their A/Sn and F1 counterparts produced more IFN-γ following infection. F1 cells overall expressed an intermediate phenotype between the two parental strains. Such a more balanced type of immune reactivity could be linked to a better TB defense.