Helminth species specific expansion and increased TNF-alpha production of non-classical monocytes during active tuberculosis

Abstract

Both Mycobacterium tuberculosis infection and helminths may affect innate immune mechanisms such as differential effects on monocytes towards the non-classical and intermediate subsets that favor bacterial persistence. Our aim, was to investigate helminth species specific effects on the frequency and functional activity of monocyte subsets in patients with active tuberculosis and healthy subjects. HIV-negative patients with active pulmonary tuberculosis (PTB) and community controls (CCs) in Gondar, Ethiopia were screened for helminth infection by stool microscopy. Flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) and ex vivo stimulation with purified protein derivative (PPD) and helminth antigens were used to characterize the distribution of monocyte subsets and their function. A total of 74 PTB patients and 57 CCs with and without helminth infection were included. Non-classical monocytes were increased in PTB patients with Ascaris and hookworm infection but not in Schistosoma-infected patients. Ascaris had the strongest effect in increasing the frequency of non-classical monocytes in both PTB patients and CCs, whereas PTB without helminth infection did not affect the frequency of monocyte subsets. There was a helminth specific increase in the frequency of TNF-α producing non-classical monocytes in hookworm infected PTB patients, both with and without PPD-stimulation. Low-to-intermediate TB disease severity associated with increased frequency of non-classical monocytes only for helminth-positive PTB patients, and the frequency of TNF-α producing monocytes were significantly higher in intermediate and non-classical monocytes of helminth positive PTB patients with an intermediate disease score. Helminth infection affected the frequency of monocyte subsets and function both in TB patients and controls which was helminth species dependent in TB patients. The clinical role of this potential immunomodulatory effect needs further study and may affect the response and protection to tuberculosis in areas where helminth infections are endemic.

Patterns of SARS-CoV-2 exposure and mortality suggest endemic infections, in addition to space and population factors, shape dynamics across countries

“…Interestingly though, hookworm is not endemic in the Americas [45] and we found a more direct effect of the prevalence of this helminth, reducing the number of deaths attributed to SARS-CoV-2. Heterogeneity in the relationships between helminth species and other pathogens such as malaria or tuberculosis in coinfections are well understood [46,47] so it is not surprising that we see this for SARS-CoV-2. Examining regional patterns in helminth coinfections as well as focussed case-control studies will likely further clarify the nature of these potentially complicated relationships.…”

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

“…In TB patients, on the other hand, there were lower Th1 and Th17 responses mainly during hookworm infection. We previously demonstrated that helminth-mediated expansion of non-classical monocytes in TB patients was species-dependent [ 29 ]. Thus, although the sample size for a species subgroup analysis was low, our data shows that helminth-induced modulation of cytokine response is affected in a species-specific manner.…”

“…A limitation in our study was that the sample size for helminth species subgroup analysis was small especially in the A. lumbricoides positive groups. The helminth egg intensity in the majority of helminth positive CCs and TB patients were low [29] which might have an impact to verify the immunological consequence of helminths but is also explained by the procedure to exclude symptomatic helminth infection. Hookworm single positive CCs were very limited in this study.…”

“…stercoralis and Wuchereria bancrofti infections, in active TB patients, suppressed the production of systemic IFN-gamma, TNF-alpha, IL-2, IL-17A and IL-17F [ 7 ]. These studies indicate that helminths impair TB protective immunity, however, the species-specific effects of different helminth species are rarely investigated [ 28 , 29 ] and need further investigation in areas where both TB and helminth infections are endemic. Therefore, our aim was to investigate the species-specific effect of helminths on the production of Th1, Th2, Th17 and the regulatory cytokine IL-10 in CCs and newly diagnosed pulmonary TB patients in Gondar, Ethiopia.…”

Identificação de um novo conjunto de biomarcadores para predição do curso da infecção pelo >i<Mycobacterium tuberculosis>/i<

“…As células T juntam-se então aos neutrófilos e macrófagos constantemente recrutados ao sitio inflamatório, e ao redor dos macrófagos alveolares infectados, forma-se o granuloma(PAI et al, 2016).Essa estrutura composta por diversos tipos de células imunes produzindo mediadores inflamatórios e microbicidas tem como principal função impedir que a bactéria se dissemine e eliminar o foco de bactérias do centro do granuloma(PAI et al, 2016).Os monócitos são uma das principais células imunes que compõem o granuloma, e migram ao sitio de infecção em resposta às citocinas e quimiocinas liberadas pelas células residentes que reconhecem as bactérias(FLYNN;CHAN;LIN, 2011;ORME;BASARABA, 2014). Os monócitos são elementos fundamentais da resposta imune inata primária, e sua importância é relatada em estudos relacionados ao câncer (CAMPBELL; KUO, 2020), ao HIV (DEPABLO-BERNAL et al, 2020), infarto agudo do miocárdio(CHEN et al, 2021), Covid-19 (JAFARZADEH et al., 2020, infecções helmínticas(BEWKET et al, 2021), dentre outros.Na tuberculose, os monócitos são descritos como tendo papel antagônico. Sua principal função é a defesa antimicrobiana por meio de ativação dos mecanismos microbicidas inatos e a indução da imunidade adquirida contra o Mtb(PAHARI et al, 2018).…”