Embracing microbial exposure in mouse research

Abstract

Research using mouse models have contributed essential knowledge toward our current understanding of how the human immune system functions. One key difference between humans and typical laboratory mice, however, is exposure to pathogens in their respective environments. Several recent studies have highlighted that these microbial encounters shape the development and functional status of the immune system. For humans, such numerous and unavoidable encounters with viruses, bacteria, and parasites may be a defining factor in generating a healthy and robust immune system, poised to respond to new infections and to vaccination. Additionally, the commensal organisms that make up the host microbiome also change with environment and impact the immune response. Hence, there is a pressing need to generate more faithful mouse models that reflect the natural state of the human immune system. This review explores the use of new experimental mouse models designed to better understand how host-microbial interactions shape the immune response. By embracing these technologies to complement traditional mouse models, researchers can remove a significant barrier that has long separated murine and human immunologists.

Keywords: host-pathogen interactions; immune response; microbiome; mouse models.

FIGURE 1. Cohousing with wild mice.

Cohousing of SPF mice with outbred wild mice results in the transfer of pathogens and commensal microbes to the SPF animals. Given time, these naturally acquired bacterial, viral, and parasitic infections change the immune system of the cohoused mice. C57BL/6 mice shift from a naïve immune status resembling a newborn infant, to a more mature, antigen experienced immune system resembling adults. These changes alter both the composition and functionality of the murine immune system

FIGURE 2. Wild microbiome transfer.

Colonization of germ-free mice with wild mouse microbiomes results in a diversified gut microbiota that is stably transferrable within a colony throughout multiple generations. First, wild mice were captured and their microbiomes were screened and biobanked to be used as donors. Iliocecal material was transferred (from donors that were found to be pathogen-free) via oral gavage into germ-free laboratory mice to colonize the gut. Pregnant wild microbiome female mice passed their new microbiome to progeny to establish a stable colony of animals containing a wild microbiota. For comparison, SPF ileocecal material was used to reconstitute germ-free animals with a standard laboratory mouse microbiome. Wild reconstituted mice developed a diverse gut microbiome and systemic changes to the immune system