Comparison of Immune Function in Two Strains of Mice Infected with Heligmosomoides bakeri after Calorie Restriction

Direct calorie restriction (CR) or CR mimetics can potentially become therapies for many autoimmune and degenerative diseases, and studies are currently underway to test the use of CR by people. However, relatively little is known about the relationship between CR and response to pathogen infection. In this study I subjected laboratory mice (Mus musculus) to long term CR prior to infecting them with the intestinal nematode (roundworm) Heligmosomoides bakeri for 2, 4 or 6 weeks. Immune responses were measured in slow-responding (C57BL/6) and fast responding (SJL) mouse strains. Overall, my study showed that both C57 and SJL mice used cellular and immunoglobulin responses against H. bakeri, but the robustness, timing, and the effect of CR on those responses varied between the strains. The cellular responses fluctuated in C57 mice, with peaks at 2 (neutrophil numbers) and 4 weeks (eosinophil numbers, levels of mucosal mast cell protease-1 [mMCP-1]), but were similar for all infection durations in SJL mice. As expected, CR had no effect on eosinophils, but it did invigorate production of neutrophils. Interestingly, in C57 mice the invigorating effect of CR on neutrophils was observed only in the presence of infection, while the invigorating effect of CR on mMCP-1 was observed only in the absence of infection. CR invigorated white blood cell responses regardless of infection in SJL mice, but it attenuated their mMCP-1 response. SJL mice may rely more on reactive oxygen species (ROS) which could have caused SJL to compensate for a CR-mediated decrease in other ROS by producing more ROS-producing neutrophils even in the absence of infection. SJL mice had a less robust mMCP-1 response than C57 mice, and this response was further attenuated by CR. Regarding immunoglobulin responses, my study showed that C57 had more robust non-specific responses (IgA and total IgG1), while the parasite – specific response (H. bakeri-specific IgG1) was similar in both strains. While CR invigorated IgA in C57 mice, it either had no effect, or an attenuating effect in SJL. CR had an attenuating effect on total IgG1 in both C57 and SJL mice, but CR had no effect on the H. bakeri-specific IgG1 response in either strain. Taken together, my study shows that calorie restriction can have both invigorating, attenuating, and no effect on various components of the immune system depending on mouse strain, with potentially important implications on the future CR and CR mimetics therapies for humans.