Intraperitoneal administration of the anti-IL-23 antibody prevents the establishment of intestinal nematodes in mice

Abstract

Previous studies have established that an increased Th-9 response creates a hostile environment for nematode parasites. Given that IL-23, a cytokine required for maintenance of the IL-17–secreting phenotype, has inhibitory effects on IL-9 production, we hypothesized that reducing circulating IL-23 by treatment with anti-IL-23 antibodies would reduce the establishment and development of parasitic intestinal nematodes. In this study, we show that animals treated with anti-IL-23 monoclonal antibodies showed a drastic reduction in the number of mouse pinworms (Aspiculuris tetraptera) recovered from the intestine (p < 0.001) at 23 days post-infection compared to the untreated animals. The cytokine levels in Peyer’s patches (PP) in treated and infected animals increase the expression of interleukins such as IL-25, IL-21, and IL-9, augmenting mucus production in the crypts, and boosting chemokines, such as OX40 and CCL20 in the mucosa. Our results suggest that the Th17/Th2 regulatory mechanism provoked by the administration of the anti-IL-23 antibody prevents the implantation of the intestinal nematode in mice. The diminished inflammatory IL-17 levels alter the Th9 environment perhaps as a consequence of IL-17 inhibiting IL-9 expression. These Th9 conditions may explain the successful treatment against Inflammatory Bowel Disease (IBD) both with antibodies against IL-23 or through parasitization with nematodes.

Deficiency of G protein‐coupled receptor Gpr111/Adgrf2 causes enamel hypomineralization in mice by alteration of the expression of kallikrein‐related peptidase 4 (Klk4) during pH cycling process

“…Images were captured using an LSM 700 confocal microscope (Zeiss, Jena, Germany). Fluorescence intensity was measured using ImageJ software (NIH, MA, USA) as previously described 27 . The layer of ameloblasts in the mandibular first molars was set as the region of interest and the mean intensity was measured.…”

“…Fluorescence intensity was measured using ImageJ software (NIH, MA, USA) as previously described. 27 The layer of ameloblasts in the mandibular first molars was set as the region of interest and the mean intensity was measured. The background intensity was then subtracted from the mean intensity.…”

Interleukin (IL)-21 in Inflammation and Immunity During Parasitic Diseases

“…IL-21 was detectable following infection of mice with a natural murine intestinal nematode, Heligmosomoides polygyrus (Espitia et al, 2010; Ariyaratne et al, 2018). The expression of IL-21 in another murine model of intestinal nematodiasis, caused by the mouse pinworm, Aspiculuris tetraptera , was tissue-dependent and significantly higher levels of IL-21 transcripts were measured in the Peyer's patches (PP), and to a lesser extent in the spleens and in the mesenteric lymph nodes, of wild-type mice infected with A. tetraptera (Gomez-Samblas et al, 2018). Mice deficient for a functional IL-21/IL-21R axis failed to elicit anti-helminth-specific IgG 1 responses and subsequently were unable to clear helminth infection as compared with their wild-type counterparts (King et al, 2010).…”

Single Nucleotide Polymorphism Effects on Lamb Fecal Egg Count Estimated Breeding Values in Progeny-Tested Katahdin Sires

“…Changes in IL12B that result in down-regulation of IFNγ may therefore favor Th2 cell differentiation. Administration of anti-IL-23 antibodies prevented implantation of intestinal nematodes in mice ( Gomez-Samblas et al, 2018 ).…”