At Homeostasis Filarial Infections Have Expanded Adaptive T Regulatory but Not Classical Th2 Cells

Abstract

Despite the well-documented immune suppression associated with human helminth infections, studies characterizing the immune response at the single-cell level are scanty. We used multiparameter flow cytometry to characterize the type of effector (Th1, Th2, and Th17) and regulatory (natural T regulatory cells [nTregs] and adaptive Treg cells [aTreg/type 1 regulatory cells (Tr1s)]) CD4+ and CD8+ T cells in filaria-infected (Fil+) and -uninfected (Fil−) individuals at homeostasis (in the absence of stimulation). Frequencies of CD4+ lymphocytes spontaneously producing IL-4, IL-10, and IL-17A were significantly higher in Fil+, as were those of IL-10+/IL-4+ double-producing CD4+ cells. Interestingly, frequencies of Th17 and aTreg/Tr1s but not classical Th1 or Th2 cells were significantly increased in Fil+ compared to Fil− individuals. Although the frequency of nTreg was increased in Fil+, IL-10 was overwhelmingly produced by CD4+CD25− cells. Moreover, the concentration of IL-10 produced spontaneously in vitro strongly correlated with the integrated geometric mean fluorescence intensity of IL-10–producing aTreg/Tr1s in Fil+. Together, these data show that at steady state, IL-10–producing aTreg/Tr1 as well as nTreg and effector Th17 CD4+ cells are expanded in vivo in human filarial infections. Moreover, we have established baseline ex vivo frequencies of effector and Tregs at homeostasis at a population level.

Decreased Prevalence of Lymphatic Filariasis Among Subjects with Type-1 Diabetes

“…It is surprising that T1DM (an autoimmune disorder) and T2DM (a metabolic disorder), despite completely different underlying mechanisms for glucose intolerance, are modulated by LF infection. However, T1DM and T2DM are characterized by the presence of an intense inflammatory milieu, and filarial infections are known inducers of regulatory networks including regulatory T cells, 29,30 tolerogenic dendritic cells, 31 alternatively activated macrophages, 32 and anti-inflammatory cytokines. 33 Thus, it is not surprising that filarial infections exert such a profound effect on the prevalence of diabetes mellitus of autoimmune and metabolic origin.…”

Inmunorregulación inducida por helmintos: una actualización

“…En este sentido, de una manera estricta no se puede generalizar sobre los efectos de los helmintos en la respuesta inmunológica a partir del hallazgo obtenido con una especie; sin embargo, hay poblaciones celulares que están ampliamente relacionadas con la infección por helmintos independientemente del tipo de parásito. Los linfocitos T reguladores (Treg) son un buen ejemplo de este tipo de blanco del sistema inmunológico que tienen los helmintos (10). Para otras poblaciones descritas de manera más reciente, tales como los linfocitos B reguladores, se necesitan más estudios en diferentes contextos de infección para conocer la universalidad del efecto inmunomodulador (11).…”

“…Es amplia la evidencia científica que respalda el efecto inductor de varias helmintiasis sobre los Treg (10,12). Además del fenotipo clásico de los Treg provenientes del timo (CD4 + CD25 + FOXP3 + ) se han descrito otras poblaciones circulantes productoras de IL-10 (Tr1) o TGF-β (10,13).…”

Human Helminths and Allergic Disease: The Hygiene Hypothesis and Beyond

“…77 It has been demonstrated that IgG can intercept allergen before it binds to IgE present on membranes of mast cells and basophils, 74 and that allergenIgG complexes can deactivate target cell by activation of the inhibitory Fc receptor (FcγRIIb), that in turn activates phosphatases in the molecular cross-linking regions of IgE shutting down FcεRI signaling. 78,79 A more unifying explanation suggests that IL-10, a primarily T-cell-derived cytokine commonly induced in chronic helminth infection, [80][81][82] may underlie the protection from SPT positivity. 11,83 Indeed, it is believed that the IL-10 modified Th2 response may be responsible for the parasite-antigen-specific tolerance imprinted on the host by helminth infection.…”

“…11,83 Indeed, it is believed that the IL-10 modified Th2 response may be responsible for the parasite-antigen-specific tolerance imprinted on the host by helminth infection. 80,84,85 Parasite-induced IL-10 or other regulatory mechanisms-that can involve cell populations such as Tregs 81,86 and Bregs…”