Increased frequency of Th2-type cytokine-producing T cells in microfilaremic loiasis.

Abstract

Abstract. The frequency of cytokine-producing peripheral blood mononuclear cells was assessed in 28 subjects with microfilaremic loiasis and in 14 amicrofilaremic individuals. In addition, a subgroup of seven microfilaremic individuals coinfected with Plasmodium malariae was evaluated. By using flow cytometry for the intracellular detection of cytokines, a more pronounced T helper (Th)2 cell-type response with the expansion of interleukin (IL)-4, IL-10, and IL-13 expressing CD4 ϩ cells in the microfilaremic compared with the amicrofilaremic group was noted. Expression of IL-5 was equivalent in both groups as was the frequency of Th2-type cytokines expressing CD8 ϩ cells and of Th1-type cytokines (interferon [IFN]-␥, IL-2, IFN-␥/IL-2) producing CD4 ϩ and CD8 ϩ cells. Th0-type cytokineexpressing cells, represented by IL-4/IFN-␥, IL-10/IFN-␥, and IL-13/IFN-␥, were equally distributed within groups. Coinfection of P. malariae did not significantly alter the cytokine expression compared with microfilaremic individuals without P. malariae infections. By identifying a large panel of cytokine-producing T cell subpopulations, a Th2-driven immune response in microfilaremic Loa loa patients was noted.Loiasis is a parasitic infection caused by the filarial nematode Loa loa, which is endemic in rain forest areas of Central and West Africa. Infective larvae are transmitted by diurnal bites of flies of the genus Chrysops and, over a period of several months, develop into mature, adult worms that may liberate microfilariae into the bloodstream. Among individuals infected with L. loa, clinically distinct subgroups can be identified with manifestations ranging from asymptomatic microfilaremia to a hyperresponsive state characterized by more frequent episodes of local angioedema (Calabar swellings) and pronounced eosinophilia in the absence of microfilariae. In endemic areas, only a minority of infected people have detectable microfilariae in blood. 1 However, the majority of infected subjects, including most visitors to endemic areas, remain amicrofilaremic and are more likely to have a hyper-responsive syndrome. 2 The apparent differences in clinical presentation are thought to reflect the diversity of the immune response of the host to filarial antigen, with diminished humoral and cellular reactivity in the presence of circulating microfilariae. Most previous results on L. loa-host relationship were derived from studying temporary residents of areas of endemicity. These amicrofilaremic patients had elevated serum parasite-specific immunoglobulin (IgE and IgG) levels, augmented filaria-specific lymphocyte proliferative responses, and an increase in the ratio of CD4 ϩ /CD8 ϩ T cells. 3,4 Immune mechanisms activated in individuals continuously exposed to infection have been studied far more extensively in other filarial species. In particular, the categorization of T helper (Th) cells into at least two functionally different subsets on the basis of their cytokine profiles has provided a useful framework for the understanding of im...

African-European differences in the capacity of T-cell cytokine production.

“…The exclusive induction of a Type 1 cytokine response in lymphocytes during measles has recently been reported. 13 Common parasites such as helminths or even malaria that preferentially initiate a Type 2-biased immune response, as recently pointed out, 8,14 are virtually absent in Europe and Japan. Thus, it is not surprising that the frequency of IL-4-and IL-13-expressing T cells remains at a low level throughout life in nonatopic people from these regions.…”

“…Fourteen adults (9 women, 5 men; median age, 31 years; age range, 20-63 years) and 8 children (4 girls, 4 boys; median age, 8 years; age range, 4-12 years), all apparently healthy and nonatopic Gabonese people or, in the case of children, their parents or guardians, were asked to participate when they met the following study criteria: no recent history of malaria or other systemic infections; no recent intake of any medication; normal presentation at physical examination, no clinical signs and symptoms; levels of the acute-phase reactant C-reactive protein below the level of detection (measured by immunonephelometry; Behring, Vienna, Austria). Carriers of Loa loa microfilariae have been shown to be associated with a more pronounced Type 2 response in comparison to amicrofilaremics 8 ; therefore, such people were excluded from further analyses. The presence of malarial parasites was dis- closed by the examination of Giemsa-stained thick blood smears; concurrent microfilaremia was excluded by Giemsastained thick blood smears, leukoconcentration, and Nuclepore filtration methods.…”

Microfilarial distribution of Loa loa in the human host: population dynamics and epidemiological implications

“…While genetic epidemiology (Garcia et al 1999) and immunological studies (Winkler et al 1999 ;Akué et al 2002 ;Walker-Deemin et al 2004) have brought useful insights into understanding the processes leading to some individuals developing L. loa microfilaraemia, the population dynamics of L. loa remains poorly documented. In a previous paper, we presented a detailed analysis of the structure of the microfilarial reservoir of L. loa in an endemic population through the study of host age-and sexspecific parasitological profiles in terms of prevalence and intensity of microfilaraemia (Pion et al 2004).…”

Associations Between Helminth Infections, Plasmodium falciparum Parasite Carriage and Antibody Responses to Sexual and Asexual Stage Malarial Antigens

“…7,8 The immunological protection against clinical malarial episodes is associated with a more pronounced Th1 response 9 and with the production of cytophilic antibodies (immunoglobulin G [IgG]1 and IgG3). 10,11 However, the immune phenotype of helminth-infected subjects is generally characterized by a Th2 skewed response 12,13 and is marked by the production of noncytophilic IgG (IgG4) and immunoglobulin E antibodies.…”