Role of Interleukin-4 (IL-4) and IL-10 in Serum Immunoglobulin G Antibody Responses following Mucosal or Systemic Reovirus Infection

Abstract

Mucosal and parenteral immunizations elicit qualitatively distinct immune responses, and there is evidence that mucosal immunization can skew the balance of T helper 1 and T helper 2 responses. However, a clear picture of the effect of the route of infection on the balance of the T helper responses has not yet emerged. Our laboratory previously demonstrated that oral reovirus infection elicits specific serum immunoglobulin G2a (IgG2a), while parenteral reovirus infection elicits the mixed production of specific serum IgG2a and IgG1 in mice of the H-2 d haplotype. Knowing that IgG2a production is indicative of a T helper 1 response and IgG1 production is indicative of a T helper 2 response, we hypothesized that the route of infection influences the development of T helper 1 and T helper 2 responses. Using quantitative reverse transcription-PCR, we found that mRNA for the T helper 1 cytokines gamma interferon and interleukin-12 (IL-12) were expressed in draining lymphoid tissues following both oral and parenteral infections. However, we observed that mRNA for the T helper 2 cytokine IL-10 was suppressed in the Peyer's patches and mesenteric lymph nodes and IL-4 mRNA was suppressed in the mesenteric lymph nodes compared to noninfected controls, following oral infection. Using recombinant cytokines and cytokine knockout mice, we confirmed that IL-4 plays a major role in mediating the route-of-infection-dependent differences in serum IgG subclass responses. Therefore, the route of infection needs to be taken into consideration when developing vaccines and adjuvant therapies.

Experimental intestinal reovirus infection of mice

“…Interestingly, other studies have described suppressed IL-10 activity in PP of mice infected with reovirus serotype 1 [67]. Those differences may reflect the fact that our studies were done using IELs from intestinal tissues after removal of PPs, or alternatively that virus strain differences influence the outcome of IL-10 production in the small intestine.…”

“…Differences also exist in the levels of IFN-γ produced by lymph node cells following intradermal infection, with C3H mice being high producers and BALB/c, C57BL/6, and B10.D2 mice being low responders [39]. IFN-γ and IL-12 mRNA levels increase in draining popliteal or mesenteric lymph nodes following footpad or oral infection with reovirus serotype 1, respectively [67].…”

3,3′-Diindolylmethane stimulates murine immune function in vitro and in vivo

“…The mechanisms for host resistance to viruses are multifactorial, including innate and acquired immune components. Immune responses to enteric reovirus infection in murine gastrointestinal-associated lymphoid tissues have been well characterized relative to (a) cell-mediated immunity [27,54], (b) expression of virus-specific intestinal IgA [25,27,55], (c) serum IgG level [55,56] and (d) cytokine production [57,58]. These characteristics make reovirus useful in studying the effects of immunomodulatory compounds on viral infection in vivo [59,60].…”

The liquid culture filtrates of Paecilomyces tenuipes (Peck) Samson (=Isaria japonica Yasuda) and Paecilomyces cicadae (Miquel) Samson (=Isaria sinclairii (Berk.) Llond) regulate Th1 and Th2 cytokine response in murine Peyer's patch cells in vitro and ex vivo

“…7). IL-10, one of the cytokines produced by Th2, strongly suppresses the activation of monocytes and Th1 lymphocyte immune responses [20]. Since PTCF and PCCF did not inhibit the production of IL-5 and IL-4, that are also Th2 cytokines, (Figs.…”

“…Since IL-10 is a key cytokine produced by a multitude of mucosal immune effector cells and thought to be a Th2 cytokine [20], we next investigated the influence of PTCF and PCCF on IL-10 production in the PP cells in vitro and ex vivo. Both PTCF and PCCF increased the production of IL-10 in the PP cells irrespective of Con A stimulation in vitro ( Fig.…”