Long-term persistence of cellular hyporesponsiveness to filarial antigens after clearance of microfilaremia.

Abstract

Abstract. The persistence of parasite-specific cellular hyporesponsiveness after clearance of blood microfilariae (mf) was studied in 18 individuals who had been treated with a single dose of ivermectin, diethylcarbamazine, or a combination 2-3 years previously and who had initially cleared their parasitemia. At recruitment into the present study, 50% were again mfϩ and 50% remained mfϪ. There were no significant differences between the mfϩ and mfϪ groups in the amount of interferon-␥ (IFN-␥) produced by peripheral blood mononuclear cells in response to adult or microfilarial antigens, although IFN-␥ production in response to purified protein derivative was greater in the mfϩ group (geometric mean [gm] ϭ 3,791 pg/ml; P ϭ 0.02) than in the mfϪ group (gm ϭ 600 pg/ml). These data suggest that although microfilaremic individuals may temporarily regain the ability to produce IFN-␥ to parasite antigens post-treatment, they subsequently revert to a state of hyporesponsiveness to mfϪcontaining antigens that appears to be independent of the recurrence of microfilaremia and the response to nonparasite antigens.The clinically asymptomatic microfilariae (mf)-positive group of Wuchereria bancrofti-infected individuals has been of particular immunologic interest because of the relatively sparse inflammatory response seen despite the high intravascular parasite burden. Peripheral blood mononuclear cells (PBMCs) from the majority of individuals with subclinical microfilaremia display an inability to proliferate or produce interferon-␥ (IFN-␥) to filarial adult, mf, or larval antigens.

Protective immunity in human lymphatic filariasis: problems and prospects

“…However, the cause-effect relationship between these in vitro parameters and clinical and infection status of the hosts are still not clear. Reversal of responses observed after chemotherapy was also found to be only transient and the hyporesponsiveness reestablished after a period of time [9]. These limited but valuable studies have shown that qualitatively the immune response phenotypes are sustained in both the cohorts over 13-18 years.…”

Withania somnifera chemotypes NMITLI 101R, NMITLI 118R, NMITLI 128R and withaferin A protect Mastomys coucha from Brugia malayi infection

“…Our findings thus suggest that stimulation of both Th1‐ and Th2‐helper immune response provide better degree of protection than either a Th1‐ or Th2‐biased stimulation. Immunosuppression has been earlier reported to be accompanied with invasion of infective filarial larvae facilitating their establishment in the vertebrate host (30–34). The immunostimulation provided by withaferin A and different chemotypes during infection mounted sufficient resistance or at least neutralized to some extent the immunosuppression brought about by the invading larvae interfering with its establishment, further growth and development.…”

Effect of chemotherapeutic treatment on cytokine (IFN-γ, IL-2, IL-4, IL-5, IL-10) gene transcription in response to specific antigens in Brugia malayi-infected Mastomys coucha

“…Nevertheless, and corresponding with our results, Sartono et al (1995) reported an enhanced IFN-γ response of PBMC to specific antigen in Wuchereria bancrofti patients 1 year after DEC application and Henry et al (2001) found increased IL-5 and IFN-γ responses associated with reduced IL-10 synthesis in reaction to specific antigens in ivermectintreated Onchocerca volvulus patients (although >10 years after drug application). In addition, enhanced Th 1 responses were found in onchocerciasis patients, beginning 6 months after ivermectin treatment in spite of persisting microfilariae in the skin in most cases (Gopinath et al 1999). Others could not find any difference in the IFN-γ response to specific antigens between lymphatic filariasis patients found microfilaremic or amicrofilaremic 2-3 years after ivermectin-DEC treatment.…”