Helminth species dependent effects on Th1 and Th17 cytokines in active tuberculosis patients and healthy community controls

Abstract

Despite that the impact of different helminth species is not well explored, the current dogma states that helminths affect the Th1/Th2 balance which in turn affects the risk of tuberculosis (TB) reactivation and severity of disease. We investigated the influence of helminth species on cytokine profiles including IL-17A in TB patients and healthy community controls (CCs). In total, 104 newly diagnosed pulmonary TB patients and 70 HIV negative and QuantiFERON negative CCs in Gondar, Ethiopia were included following helminth screening by stool microscopy. Plasma samples and ex vivo stimulation of peripheral blood mononuclear cells (PBMCs) with purified protein derivative (PPD) and Staphylococcus enterotoxin B (SEB) was used to determine cytokine profiles by cytometric bead array. In CCs, Ascaris lumbricoides or Schistosoma mansoni infections were associated with an impaired Th1-type response (IFN-gamma, IL-6 and TNF-alpha) in PBMCs mainly with SEB stimulations, whereas in TB patients only hookworm infection showed a similar pattern. Among CCs, the IL-17A response in PBMCs stimulated with SEB was higher only for S. mansoni, whereas in TB patients, the elevated systemic IL-17A plasma level was significantly suppressed in hookworm infected TB patients compared to patients without helminth coinfection. Following treatment of TB and helminth infection there was a general decrease in ex vivio IL-10 and TNF-alpha production in unstimulated, PPD or SEB stimulated PBMCs that was the most pronounced and significant in TB patients infected with S. mansoni, whereas the follow-up levels of IFN-gamma and IL-17A was significantly increased only in TB patients without helminth coinfection from PBMCs stimulated mainly with SEB. In summary, in addition to confirming helminth specific effects on the Th1/Th2 response before and after TB treatment, our novel finding is that IL-17A was impaired in helminth infected TB patients especially for hookworm, indicating a helminth species-specific immunoregulatory effect on IL-17A which needs to be further investigated.

Activation dynamics of antigen presenting cells in vivo against Mycobacterium bovis BCG in different immunized route

“…The Th1/Th2 balance affects the outcomes of TB infection, CD4 + T cell cytokine expression pattern was associated with alterations in the systemic levels of Th1 and Th2 cytokines [ 26 ]. When mice were i.v or s.c immunized, splenic or inguinal LN mononuclear cells showed enhanced production of IL-6, IL-10, IFN-γ and TNF-α, while IL-17 only expressed highly in inguinal LN mononuclear cells.…”

Immunopathology in human pulmonary tuberculosis: Inflammatory changes in the plasma milieu and impaired host immune cell functions

“…Only a few cytokines show an unambiguous picture of being either higher or lower in tuberculosis patients' plasma. Particularly, frequently studied candidate cytokines, such as TNF‐α or IFN‐γ, were elevated in the plasma of tuberculosis patients in several studies [20, 23–26, 29, 30, 32, 37, 44, 45, 47, 57, 60, 62, 68–71], but either or both did not differ in other studies [7–10, 14, 15, 18, 20, 21, 23–26, 29–32, 37, 40, 42, 44–47, 51–54, 57, 60–64, 68–71] (Figure 1b). Insufficient study cohort sizes and low statistical power in some studies likely contribute to heterogeneity, but this does not sufficiently explain differences.…”

“…However, to provide an overview of candidates, we screened studies based on a case/control design comparing ‘plasma’ or ‘serum’ samples from patients with pulmonary tuberculosis (before treatment) and matched controls. Sixty studies were identified that meet these criteria [7–66]. The selection criteria used for the definition of ‘controls’ varied between the studies, and this is at least partially due to a missing gold standard for the classification of ‘controls’ in human tuberculosis.…”

Cytokine Responses during Mycobacterium tuberculosis H37Rv and Ascaris lumbricoides Costimulation Using Human THP-1 and Jurkat Cells, and a Pilot Human Tuberculosis and Helminth Coinfection Study

“…There is a significant geographic overlap between TB and helminth infection, particularly in low and middle-income countries (LMICs), with 20–35% of people being co-infected [ 4 ]. The impact of helminths on cell-mediated immunity has been the subject of numerous investigations [ 5 , 6 , 7 , 8 , 9 ]. However, it is still unclear if parasite infection is associated with TB activation from a dormant condition to active disease development [ 5 ].…”

“…However, in some studies, helminths were demonstrated to have no impact on human tuberculin skin tests [ 19 ], Mtb infection [ 20 ], or the improvement of TB disease management [ 20 ]. Therefore, reports on TB immune responses in cases of helminth coinfection are variable and dependent on the infecting parasite and the type of study [ 8 , 9 , 21 ]. Studies involving Nippostrongylus brasiliensis (Nb) and mycobacterial coinfection in mice yielded divergent findings on Mtb growth control.…”