IL-10- and TGFβ-mediated Th9 Responses in a Human Helminth Infection

Background

Th9 cells are a subset of CD4⁺ T cells that express the protoypical cytokine, IL-9. Th9 cells are known to effect protective immunity in animal models of intestinal helminth infections. However, the role of Th9 cells in human intestinal helminth infections has never been examined.

Methodology

To examine the role of Th9 cells in Strongyloidis stercoralis (Ss), a common intestinal helminth infection, we compared the frequency of Th9 expressing IL-9 either singly (mono-functional) or co-expressing IL-4 or IL-10 (dual-functional) in Ss-infected individuals (INF) to frequencies in uninfected (UN) individuals.

Principal Findings

INF individuals exhibited a significant increase in the spontaneously expressed and/or antigen specific frequencies of both mono- and dual-functional Th9 cells as well as Th2 cells expressing IL-9 compared to UN. The differences in Th9 induction between INF and UN individuals was predominantly antigen-specific as the differences were no longer seen following control antigen or mitogen stimulation. In addition, the increased frequency of Th9 cells in response to parasite antigens was dependent on IL-10 and TGFx since neutralization of either of these cytokines resulted in diminished Th9 frequencies. Finally, following successful treatment of Ss infection, the frequencies of antigen-specific Th9 cells diminished in INF individuals, suggesting a role for the Th9 response in active Ss infection. Moreover, IL-9 levels in whole blood culture supernatants following Ss antigen stimulation were higher in INF compared to UN individuals.

Conclusion

Thus, Ss infection is characterized by an IL-10- and TGFβ dependent expansion of Th9 cells, an expansion found to reversible by anti-helmintic treatment.     

Isolation and Characterization of Antimicrobial Cyclic Dipeptides from Pseudomonas fluorescens and Their Efficacy on Sorghum Grain Mold Fungi

This study was aimed at isolation and characterization of natural antifungal compounds for grain mold, a key parasitic fungal disease of sorghum. Pseudomonas fluorescens strain isolated from rhizosphere of groundnut crop was selected as a source. Its biocontrolling ability was assessed by testing some biochemical attributes such as phosphate‐solubilization, and HCN, NH₃, indole‐3‐acetic acid, and siderophore production. The strain showed positive result for all except indole‐3‐acetic acid, revealing its suitability for a further study. The antibiotic‐sensitivity pattern of the strain against 43 antibiotics was also established, which showed resistance to 15 antibiotics. The efficacy of P. fluorescens strain against grain mold was identified by dual culture technique. Hundred percent inhibition was found against Fusarium moniliforme, an important causative agent of this disease. The strain was fermented for secondary metabolites and extracted with AcOEt. Chromatographic separation of the extract yielded four known compounds, cyclo(L ‐Pro‐L ‐Phe) ( 1 ), cyclo(trans‐4‐hydroxy‐L ‐Pro‐L ‐Leu) ( 2 ), cyclo(trans‐4‐hydroxy‐L ‐Pro‐L ‐Phe) ( 3 ), and cyclo(Gly‐L ‐Pro) ( 4 ), which were characterized by spectral analysis and optical rotation. The crude extract, a mixture of 2 and 3 , and isolated 1 were proved to be significantly effective against grain mold fungi. This is the first report on production of these cyclic dipeptides by P. fluorescens and their antagonistic properties.