Immune defense of wild-caught Norway rats is characterized by increased levels of basal activity but reduced capability to respond to further immune stimulation

Abstract

Studies of wild animals' immunity often use comparison with laboratory-raised individuals. Using such an approach, various data were obtained concerning wild Norway rat's immunity. Lower or higher potential of immune system cells to respond to activation stimuli were shown, because of analysis of disparate parameters and/ or small number of analyzed individuals. Inconsistent differences between laboratory and wild rats were shown too, owing to great response variability in wild rats. We hypothesized that wild rats will express more intense immune activity compared to their laboratory counterparts which live in a less demanding environment. To test this, we analyzed the circulating levels of inflammatory cytokine interleukin-6 (IL-6), a mediator which has a central role in host immune defense. In addition, we examined the activity of the central immune organ, the spleen, including cell proliferation and production of pro-inflammatory cytokines interferon-γ (IFN-γ) and interleukin-17 (IL-17), which are major effectors of cellular adaptive immune response. In order to obtain reasonable insight into the immunity of wild Norway rats, analysis was conducted on a much larger number of individuals compared to other studies. Higher levels of plasma IL-6, higher spleen mass, cellularity and basal IFN-γ production concomitantly with lower basal production of anti-inflammatory cytokine interleukin-10 (IL-10) revealed more intense immune activity in the wild compared to laboratory rats. However, lower responsiveness of their spleen cells' proinflammatory cytokine production to concanavalin A (ConA) stimulation, along with preserved capacity of IL-10 response, might be perceived as an indication of wild rats' reduced capability to cope with incoming environmental stimuli, but also as a means to limit tissue damage.

Physiological strategies in wild rodents: immune defenses of commensal rats

“…The immune status of wild-caught rats and house mice is analyzed mainly by comparison with laboratory strains that live in reduced environmental complexity and paucity or lack of stressful conditions. In line with differences in environmental influences between wild-caught and laboratory mice and rats, great variations in parameters of immune function were observed (Abolins et al 2011;Mirkov et al 2018).…”

“…Fewer eosinophils (as a percent of total granulocytes) (Lin et al 2012a) and lack of eosinophils (Mirkov et al 2018) in peripheral blood of wild compared to laboratory rats might be an indication of their increased turnover, as a decline of these granulocytes has been noted during inflammatory response to infection in laboratory mice (Bass 1975;Ohnmacht et al 2007). However, high white blood cell counts with a shift in favor of neutrophils and high relative numbers of monocytes were noted in more than 20% of wild rats (Kataranovski et al 2009), as well as greater representation of peripheral blood monocytes (as a fraction of total peripheral blood leukocytes) (Lin et al 2012a), which is an indication of a systemic inflammatory response established as a response to the need for newly produced cells in these individuals (Schwartz & Weiss 1991;Asimakopoulos 1999).…”

“…Higher absolute mass and cellularity found in wild versus laboratory Norway rats are indications of greater immune activity in the spleen of these individuals (Kataranovski et al 2009;Mirkov et al 2018). Increased proportion of red pulp in the wild compared to laboratory animals (Kataranovski et al 2009), as well as extramedullary hematopoiesis (EHM), found in rats with liver infection with C. hepaticum and in Leptospira-infected kidneys (Seguel et al 2017), is considered as a response to the need for a synthesis of new blood cells in these animals.…”

“…Spleen cytokine basal (unstimulated) responses in wild rats create a pro-inflammatory milieu in this lymphoid organ, judging by significantly lower ratios of anti-inflammatory/immunoregulatory cytokine (IL-10) to pro-inflammatory cytokines (interferon (IFN)-γ and IL-17) (Mirkov et al 2018). In contrast, stimulation with concanavalin A (ConA) revealed a lower capability of spleen cells from wild rats to produce IFN-γ , IL-2, and TNF (Lesher et al 2006) and IFN-γ or IL17 production (Mirkov et al 2018).…”

“…Spleen cytokine basal (unstimulated) responses in wild rats create a pro-inflammatory milieu in this lymphoid organ, judging by significantly lower ratios of anti-inflammatory/immunoregulatory cytokine (IL-10) to pro-inflammatory cytokines (interferon (IFN)-γ and IL-17) (Mirkov et al 2018). In contrast, stimulation with concanavalin A (ConA) revealed a lower capability of spleen cells from wild rats to produce IFN-γ , IL-2, and TNF (Lesher et al 2006) and IFN-γ or IL17 production (Mirkov et al 2018). Lower responsiveness of wild rat splenocyte proinflammatory cytokine production was accompanied by high production of anti-inflammatory cytokine IL-4 (Lesher et al 2006) and unchanged (preserved) immune-regulatory cytokine, IL-10 ( Mirkov et al 2018).…”