T-Helper-1 and T-Helper-2 Immune Responses in Mice Infected With the Intestinal Fluke Neodiplostomum Seoulense: Their Possible Roles in Worm Expulsion and Host Fatality

Abstract

Neodiplostomum seoulense is highly pathogenic and lethal to experimental mice; most worms are expelled within 2 mo of acquisition. In this study, T-helper (Th) cell immune responses were studied in N. seoulense-infected BALB/c mice. Spleen and mesenteric lymph node (MLN) cells of infected mice proliferated in response to parasite antigens; CD4+ T cells proliferated more than CD8+ T cells. Antigen-induced interferon (IFN)-gamma (a Th1 cytokine) secretion began to increase at day 7 postinfection (PI) in spleen and MLN cells, and this was maintained at day 28 PI, whereas interleukin (IL)-4 (a Th2 cytokine) secretion was somewhat lower. Similar results were observed for mRNA signals of IFN-gamma and IL-4. Antigen-specific serum total immunoglobulin (Ig)G, IgG1, IgM, and IgA levels (Th2-induced) were elevated from days 7 to 14 to day 28 PI, and IgG2a (Th1-induced) was elevated at days 21 to 28 PI. Interestingly, the numbers of macrophages (Th1- or Th2-induced), which were found to kill N. seoulense worms in vitro, increased remarkably during days 14-28 PI in spleens and small intestines of infected mice. This study shows that mixed Th1 and Th2 responses occur during the course of N. seoulense infection in BALB/c mice. Heavy infiltrations of macrophages in the small intestine may participate in host damage and worm expulsion.

Foodborne Intestinal Flukes in Southeast Asia

“…Whereas the serum level of IgG2a remained constant during the course of E. caproni infection, the intestinal IgG2a responses were related with worm expulsion [362]. Since IgG2a is an important element mediating T-helper-2 (Th2) immune reposnes of mice [364], the expulsion of echinostomes from the host intestine is suggested to be mediated by a Th2 immune response [362].…”

“…Binding of histamine released from mast cells to its receptors on intestinal smooth muscles would be more important than the level of histamine alone, or mastocytosis [376]. Recently, mixed Th1 and Th2 type immune responses were shown to occur during the course of N. seoulense infections in BALB/c mice, and IFN-γ(a Th1 cytokine), IL-4 (a Th2 cytokine), IgG, IgA, and IgG2a were all increased in the spleen and the small intestine [364]. Macrophages were also found significantly increased, which were found to kill N. seoulense worms in vitro [364].…”

Depressed Neuronal Growth Associated Protein (GAP)-43 Expression in the Small Intestines of Mice Experimentally Infected with Neodiplostomum seoulense

“…This parasite is a good model to study intestinal pathogenesis and pathology since it can elicit severe mucosal inflammatory responses, including mastocytosis, goblet cell hyperplasia, macrophage infiltrations, and even death of the infected mice [4-6]. Mast-cell deficient W/W v , their normal littermates +/+, C57BL/6, and C3H mice were all susceptible to death by day 23 post-infection (PI) with 200 metacercariae, with the exception of BALB/c mice, which were severely weakened but recovered after 28 days [4,7]. Their intestines showed severe anatomic and functional damage, highly suggestive of intestinal paralysis, which was irreversible in death-susceptible strains of mice [4].…”

Resistance toToxoplasma gondiiInfection in Mice Treated with Silk Protein by Enhanced Immune Responses

“…For in vitro experiments, the spleens of silk protein-administered mice were placed in sterile dishes under complete RPMI-1640 media (WelGENE Inc., Daegu, Korea) containing 10% FBS (Invitrogen, Carlsbad, California, USA), 10 mM HEPES, 2 mM L-glutamine, 2 mM sodium bicarbonate, 5×10 -5 M 2-mercaptoethanol, and antibiotics (100 IU/ml penicillin G and 100 µg/ml streptomycin; Invitrogen) and used to prepare single cells, as previously described [17]. Spleen erythrocytes were destroyed by hypotonic shock using a red blood cell lysis buffer containing NH 4 Cl, and after washing, splenocytes (1×10 6 ) were subjected to fluorescence-activated cell sorter (FACS) analysis [17].…”

“…Spleen erythrocytes were destroyed by hypotonic shock using a red blood cell lysis buffer containing NH 4 Cl, and after washing, splenocytes (1×10 6 ) were subjected to fluorescence-activated cell sorter (FACS) analysis [17]. The phenotypic ratios of CD4 + -T cells, CD8 + -T cells, macrophages, and natural killer cells were examined using a BD FACS Flow cytometer (BD Biosciences, Mountain View, California, USA).…”