Modulation of cellular immune response by cytokines in bancroftian filariasis

Abstract

Human lymphatic filariasis is a chronic helminth infection caused byWuchereria bancrofti andBrugia malayi. Wide spectrum of clinical manifestations are seen in different clinical groups of filariasis patients which comprises asymptomatic patients with circulating microfilaria (MF), individuals with chronic lymphatic obstruction (CP), Endemic normals (EN) who are asymptomatic and amicrofilaraemic or the relatively rare tropical pulmonary eosinophilia (TPE). The cellular immune response to this infection varies in different clinical groups of filarial patients. ranging from normal lymphocyte proliferative response in EN individuals to lymphocyte hyporesponsiveness in MF to total parasite antigen [Brugia malayi antigen (BMA)]. But in response to recombinant filarial antigen (pRJ51) the lymphocyte proliferation is restored in MF patients. Interestingly the lymphocytes from MFs responded normally to parasite antigen when EN serum was added in the culture whereas sera from MFs failed to revert the lymphocyte hyporesponsiveness. In order to study the molecular mechanisms responsible for parasite antigen specific lymphocyte hyporesponsiveness, we analysed both the Th1 and Th2 type cytokine gene expression profile in different clinical groups of filarasis patients. MF individuals expressed elevated Th2 type cytokines like IL-4, IL-5 and IL-10 and decreased levels of IL-2 and IFN-γ in response to parasite antigen. Chronic patients have elevated levels of both Th1 and Th2 type cytokines in response to parasite antigen. The EN individuals had a purely Th1 type pattern with absence of IL-4 and IL-5 expression. These studies clearly demonstrate the role of Th2 cytokine like IL-10 in antigen specific hyporesponsiveness seen in MF patients. Any methods to arrest the progression of this disease should concentrate on the means to revert the Th2 type into Th1 type response in the MF patients either by Th1 type cytokine therapy or by using recombinant filarial antigen which stimulates the Th1 response. Further the recombinant filarial antigen which induces Th1 type cytokine response could be used for immunoprophylactic studies.