Nonspecific immune responses and mechanisms of resistance to Eimeria papillata infections in mice

Abstract

Severe combined immunodeficient (SCID)-beige mice inoculated with the intracellular parasite Eimeria papillata produced significantly more oocysts during primary infections than inoculated immunodeficient SCID mice. Therefore, the addition of the beige mutation, which detrimentally affects neutrophil and natural killer (NK) cell functions, enhanced the parasites' ability to reproduce within the small intestine. To identify which of these two cell types is responsible for a protective immune response during primary infection, the following groups of mice were inoculated: (i) SCID mice depleted of neutrophils with antigranulocyte monoclonal antibody (RB6-8C5), (ii) C57BL/6 mice depleted of NK cells with the anti-NK-1.1 monoclonal antibody (PK136), and (iii) transgenic Tg26 ؉؉ mice (T and NK cell deficient). To identify the mechanisms of immunity during primary and secondary infections, gamma interferon (IFN-␥) knockout and perforin knockout mice were inoculated. Oocyst output was found to be significantly higher during primary infection for mice depleted of NK cells by administration of anti-NK-1.1 antibodies, for Tg26 ؉؉ mice, and for IFN-␥ knockout mice. During secondary infections, only perforin knockout mice produced significantly more oocysts compared to control mice. Our observations suggest that NK cells inhibit E. papillata oocyst output during primary infection by the production of IFN-␥ and that this inhibition is independent of perforin. Immunity to reinfection does not require IFN-␥ but appears to be mediated, at least in part, by a perforin-dependent mechanism.

Nanoselenium prevents eimeriosis-induced inflammation and regulates mucin gene expression in mice jejunum

“…The second, third, and fourth groups were orally inoculated with 1,000 sporulated oocysts of E. papillata suspended in 100 μL of distilled water. 15 The third and fourth groups received, respectively, an oral dose of 0.1 mg/kg sodium selenite (NaSe) 12 and 0.5 mg/kg SeNPs suspended in 100 μL of distilled water daily for 5 consecutive days. 7 The dose was chosen according to the results of our previous experiments ( Figure S1).…”

NK cells and apoptosis

“…Cytokine production limits parasite replication and promotes the development of adaptive cell‐mediated immunity. In the case of Eimeria papillata , resistance to reinfection does not require IFN‐γ and appears to be mediated at least in part by a perforin‐dependent mechanism 124 . Other models of parasite infection in vivo remain to be evaluated in perforin‐deficient or FasL mutant mice.…”

Genetic identification of antigens protective against coccidia

“…Studies in murine models have largely mirrored these findings, emphasizing the key role of T cells during infection (44,52–55). More specifically, the CD4+ T cell subset has been shown to play a significant role in the host immune response to primary infection with E. maxima , E. tenella and E. vermiformis but not to E. acervulina or E. papillata (43,46–48,53–55). Nonetheless control of all five species during primary infection is related to interferon gamma (IFNγ) production (43,53–58).…”

“…Characterization of the mechanisms responsible for protective immunity in the chicken against primary and secondary infection with most Eimeria species has revealed the importance of T cells (46 -48), supplemented by minor roles for B and natural killer cells (49)(50)(51)(52). Studies in murine models have largely mirrored these findings, emphasizing the key role of T cells during infection (44,(52)(53)(54)(55). More specifically, the CD4+ T cell subset has been shown to play a significant role in the host immune response to primary infection with E. maxima , E. tenella and E. vermiformis but not to E. acervulina or E. papillata (43,(46)(47)(48)(53)(54)(55).…”

“…More specifically, the CD4+ T cell subset has been shown to play a significant role in the host immune response to primary infection with E. maxima , E. tenella and E. vermiformis but not to E. acervulina or E. papillata (43,(46)(47)(48)(53)(54)(55). Nonetheless control of all five species during primary infection is related to interferon gamma (IFN γ ) production (43,(53)(54)(55)(56)(57)(58). In contrast, IFN γ is not essential for protection against secondary infection with E. vermiformis , where the requirement for specific immune mechanisms is less stringent, but remains dependent on αβ T cells in a protective response that appears to differ in requirement from that seen during primary infection (55).…”