Notice of Special Interest (NOSI): Leveraging Microbial Exposure for Improving Mouse Models of Human Immunity
Notice Number:

Key Dates

Release Date:

October 20, 2021

First Available Due Date:
February 16, 2022
Expiration Date:
January 08, 2025

Related Announcements

PA-20-195 – NIH Exploratory/Developmental Research Project Grant (Parent R21 Clinical Trial Not Allowed)

Issued by

National Institute of Allergy and Infectious Diseases (NIAID)


This Notice of Special Interest (NOSI) solicits research on immunologic characterization of mice with diverse microbial exposures (commonly referred to as “dirty mice”) to determine their usefulness as research tools to advance understanding of human immune function in homeostasis and in response to infectious or immune-mediated diseases.


Mouse models have been critical in the study of basic immunology, microbial pathogenesis, and vaccines, allowing for mechanistic insights that have been foundational for the development of therapeutics and vaccines. However, despite the utility of mice in immunological and vaccine research, there are multiple differences in immune responses between laboratory mice and humans that limit the translatability of mouse findings to humans.

“Dirty mice” (e.g., mice with diverse microbial exposures) include mice from pet stores or those captured in the wild that have been naturally exposed to a wide variety of bacterial, viral and parasitic pathogens; mice that have been specifically inoculated with pathogens that model those that commonly infect humans in early childhood; and normobiotic mice, which are generated via cecal ligation and puncture, implantation of heat-killed cecal contents, or implantation of cecal tissue. Recent studies comparing dirty mice and mice maintained under standard specific pathogen-free (SPF) conditions suggest that the presence of a diverse microbiome may account for some of the differences in immune responses between laboratory mice and humans, since microbial exposure significantly influences development and function of both the innate and the adaptive arms of the immune system. Additionally, SPF mice poorly recapitulate mature human immune responses and exhibit responses more like human neonates. In contrast, dirty mice react to immune stimuli more like human adults, making them a potentially better research tool.

Currently, dirty mice are underused by the immunology research community. A major barrier to establishing a dirty mouse colony is the cost associated with housing dirty mice in a separate facility from SPF colonies. This requirement limits an institution’s willingness to invest in establishing dirty mouse colonies, thus curtailing the insights that this mouse model may impart.

Research Objectives and Scope

This NOSI aims to stimulate research proposing to characterize immune system development, regulation and function in dirty mice via: 1) comparison of (a) mouse line(s) housed in a “clean” environment with animals housed in a “dirty” facility during homeostasis or in various infectious or immune-mediated disease models; or 2) in vitro comparison of immune profiles in primary human cells and primary cells from dirty mice. These studies will advance our understanding of the impact of a host’s microbial exposure and experience on the development and maintenance of immunity and provide the necessary data to encourage broader use of dirty mouse models in immunologic studies.

Research areas of interest include:

  • Fundamental Immunology: properties, interactions, development, and function of the innate and adaptive components (cells, molecules etc.) of the immune system during homeostasis, or in response to pathogenic infections or vaccination
  • Allergic Diseases, with a focus on asthma, rhinitis and rhinosinusitis, food allergy, and atopic dermatitis: development and persistence, genetics, identification of targets for new preventive, and therapeutic approaches
  • Autoimmunity: immunologic basis of disease, includes 1) developing a greater understanding of the fundamental immunologic principles underlying disease onset and progression, 2) developing improved animal models of disease and diagnostic tools, and 3) identifying and evaluating more effective immune-based treatment and prevention strategies
  • Transplant Immunology: elucidation of immunological mechanisms and pathways that contribute to 1) allograft rejection or tolerance in models of pancreatic islet, solid organ, or vascularized composite allograft transplantation, or 2) graft-versus-host disease in models of bone marrow/hematopoietic stem cell transplantation
  • Infectious Diseases: basic research on the fundamental mechanisms of factors impacting pathogen replication, immunopathogenesis, infection-associated expression patterns, latency, and/or persistence
  • Vaccinology: understanding how broad microbial exposure impacts safety, immunogenicity, and efficacy of vaccines

Application and Submission Information

This notice applies to due dates on or after February 16, 2022 and subsequent receipt dates through January 7, 2025.

Submit applications for this initiative using the following funding opportunity announcement (FOA) or any reissue of this announcement through the expiration date of this notice.

  • PA-20-195 NIH Exploratory/Developmental Research Grant Program (Parent R21 Clinical Trial Not Allowed)

All instructions in the SF424 (R&R) Application Guide and the funding opportunity announcement used for submission must be followed, with the following additions:

  • For funding consideration, applicants must include “NOT-AI-21-072” (without quotation marks) in the Agency Routing Identifier field (box 4B) of the SF424 R&R form. Applications without this information in box 4B will not be considered for this initiative.

Applications nonresponsive to terms of this NOSI will not be considered for the NOSI initiative.


Please direct all inquiries to the contacts in Section VII of the listed funding opportunity announcements with the following additions/substitutions:

Scientific/Research Contact(s)

Qian “Joy” Liu, M.D., MSc.
Division of Allergy, Immunology and Transplantation
National Institute of Allergy and Infectious Diseases (NIAID)
Telephone: 301-761-6621

Melody Mills, Ph.D.
Division of Microbiology and Infectious Diseases
National Institute of Allergy and Infectious Diseases(NIAID)
Telephone: 240-627-3318

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