Stimulation of TH1 Response byHelicobacter PyloriNeutrophil Activating Protein Decreases the Protective Role of IgE and Eosinophils in Experimental Trichinellosis

Abstract

Th2 responses seem to play an important role in defence against Trichinella spiralis (Ts), The Neutrophil Activating Protein of Helicobacter pylori (HP-NAP), that induces IL-12, and IL-23 expression and shifts to Thl allergen-specific Th2 cells in vitro was used as an anti-Th2 agent in BALB/c mice infected with T. spiralis. The muscle larvae (ML) burden was lower (p < 0.02) in untreated infected animals than those infected treated with HP-NAP. In both groups there was an inverse relationship between ML burden of each animal and total IgE level (controls: r -0.617,p = 0.0013 and HP-NAP-treated: r -O.678,p =0.0001) or eosinophil count, evaluated in the same mouse on day 42 (r -0.390,p = 0.0592 and r -O.803,p =0.0001, respectively). Inflammatory response around the nurse cell-parasite complex was significantly higher in HP-NAP-treated infected animals than in those untreated infected, on the contrary the number of eosinophils, counted around each complex was significantly lower in the first animal group. This study provides evidence of a powerful anti-Th2 activity in vivo by HP-NAP and for the partial protective effect of Th2 responses in T. spiralis infection.Trichinellosis is caused by the parasitic nematode Trichinella, after ingestion of raw or undercooked meat by the host. This parasite has the peculiarity of having an intracellular localization both at intestinal and muscle level where the L] larvae live and grow in a modified skeletal muscle fibre cell , called 'nurse cell ' that induces, in encapsulating Trichinella specie s, the form ation of a collagen capsule which protects the parasite from effector cells of the immune system (1). The immune response of the host at muscle level has recei ved increasing attention in recent years (2).IgE and eosinophils derived from the activation ofTh2 cells have been considered protecti ve against helminths for some time although, to date , in vivo results have provided controversial results (3-4).T helper type 2 (Th2) cells producing cytokines such as interleukin (IL)-4, IL-5, IL-9, IL-lO and IL-13 (2, 5), are not only involved in helminth infections but also in the development ofpathological conditions such as atopy and asthma (6-8).A role of the above cytokines in experimental trichinellosis has been shown; in fact IL-4 plays an important role in the development of protective responses to this parasite (9). lL-4 deficiency or lL-4 blockade delayed expulsion of Trichinella spiralis from the small intestine (7, 10-11). Like IL-4, lL-13 is an important factor during Th2 responses, mediating mechanisms similar to those induced by lL-4, such as stimulating B cell proliferation, antibody class switching to IgE and,.After binding of both IL-4 and IL-13 to IL-4 receptor a chain (lL-4Ra) signal transducer and activator of transcription factor 6 (Stat6) are phosphorylated and activated. The transcription factor Stat6, triggered by GATA3, is necessary in vivo for the expulsion of T. spiralis and for the development of eosinophilia (14).Other Th2-derived cytokines are important ...

Oral administration of recombinant Bacillus subtilis spores expressing Helicobacter pylori neutrophil‐activating protein suppresses peanut allergy via up‐regulation of Tregs

“…25 NAP can elicit high rates of IL-12, IFN-γ and IgG2a secretion, while IL-4, IL-5, IgE and IgG1 secretion are inhibited, thereby shifting the Th1/Th2 balance to a Th1-type response. 26,27 The capability to induce Th1 cytokine secretion by NAP, or other chemical agents such as recombinant IL-12, Chinese herbal medicines and turmeric, is known to be sufficient to inhibit Th2 responses and ameliorate allergic disorders. 23,28,29 Therefore, the Th1-type immune response caused by NAP and CNAP spores may be a major cause of the weakening of allergic symptoms.…”

“…The lack of IL‐4 in mice is known to lead to a decrease in IgE and IgG1 levels, as well as a reduction in peanut allergic reactions . NAP can elicit high rates of IL‐12, IFN‐γ and IgG2a secretion, while IL‐4, IL‐5, IgE and IgG1 secretion are inhibited, thereby shifting the Th1/Th2 balance to a Th1‐type response . The capability to induce Th1 cytokine secretion by NAP, or other chemical agents such as recombinant IL‐12, Chinese herbal medicines and turmeric, is known to be sufficient to inhibit Th2 responses and ameliorate allergic disorders .…”

Qualitative and Quantitative Studies of Eosinophils in Parasitic Infections

“…Through software tools, the infl ammatory infi ltrate around the nurse cell-parasite complex is measured in pixels calculating the difference between the whole area of nurse cell-parasite complex plus surrounding infl ammation and the area delimited by the collagen capsule. The infl ammatory pixel value, analyzed for more than 300 larvae per experimental group on different sections, is then converted in μm 2 (50 μm 2 = 78,478.8 pixel) [ 14 ].…”

Serum Antibodies against Helicobacter pylori Neutrophil Activating Protein in Carriers of IL-4 C-590T Genetic Polymorphism Amplify the Risk of Gastritis and Gastric Cancer

“…The most studied function for HP-NAP is recruitment and activation of neutorphils and monocytes and subsequent production of reactive oxygen intermediates[ 4 , 7 ], mediated by the activation of phagocytic NADPH-oxidase. A repertoire of other diverse functions has also been attributed to this protein which includes: (1) DNA binding[ 8 ] and protection from oxidative damage[ 6 , 9 ], (2) adhesion to mucins and mucosal surfaces[ 10 ], (3) iron-binding capability (up to 500 atoms)[ 11 ], (4) urease-independent acid resistance[ 12 ], and (5) immune activation with a pro-Th1 and anti-Th2 modulation and adjuvanticity[ 3 , 13 - 18 ] and has been demonstrated in different disease models. Host serum antibodies against HP-NAP are variably present in different populations[ 19 - 22 ] and have been associated with the risk of gastrointestinal complications including gastric cancer[ 23 , 24 ].…”