# IDO promotes severe manifestations of B. pertussis infection in infants

> **NIH NIH R21** · UNIVERSITY OF MARYLAND BALTIMORE · 2022 · $193,125

## Abstract

PROJECT SUMMARY
Immune responses to infection are dynamic, changing throughout the course of life. Pathogenic insult at early
age generates immunity that is distinct from the typical responses characterized in adults, with infants adopting
a more quiescent defense strategy that is less pro-inflammatory and more disease tolerant. This approach
benefits the infant by limiting immunopathology and the metabolic demands of generating robust inflammation,
but it also renders infants more susceptible to bacterial sepsis and severe outcomes of infectious disease.
Indoleamine 2,3-dioxygenase (IDO) drives tryptophan catabolism in the kynurenine pathway to promote a
tolerogenic immune phenotype. This molecule is highly expressed at the maternal-fetal interface where it plays
an important role in maternal tolerance to the fetus but a role for IDO in infant immunity has yet to be
determined. We hypothesize that IDO acts as a critical regulator of innate and adaptive immunity at infancy
and that actions potentiated by IDO increase infant susceptibility to infection.
 We use a Bordetella pertussis (Bp) mouse model to identify age-related responses to infection. Bp-
induced disease is most severe in infants, with the majority of infection-induced deaths occurring in those aged
<3 months. Infant Bp infection is associated with increased bacterial loads and the manifestation of systemic
pathologies that are not observed in infected adults. In an RNASeq study examining lung Bp-induced genes
that were differentially regulated by host age, we found that infection in infant mice resulted in significantly
greater Ido1 upregulation than adult infection. In addition, Bp infection increased intracellular protein
expression of IDO in lung antigen presenting cells and epithelial cells harvested from infant mice but not adult
mice. These results support the hypothesis that IDO responses are age-related, with enhanced production of
infection-induced IDO at early age. Furthermore, IDO deficiency in infant mice resulted in decreased lung
colonization by Bp and reduced leukocytosis, a critical infant-specific systemic manifestation of Bp-induced
disease. Hence, preliminary data indicates that IDO functions to enhance bacterial infectivity and pathogenesis
in infants. In this proposal, we will extend on these findings to explore the age-related kinetics of Bp-regulated
IDO induction and activity and the mechanism of IDO induction in the infant. We will also determine the impact
of IDO on other age-related outcomes of Bp pathogenesis and the effect of IDO on innate and adaptive
immune cell phenotypes. Data generated by this work will contribute to the understanding of the unique
defense strategies utilized at early age and highlight IDO as a critical regulator of infant immunity. IDO-targeted
drugs are undergoing clinical trials as cancer therapeutics; hence, if IDO depletion benefits outcomes of infant
infection, these drugs may be rapidly implemented as therapeutics for infant i...

## Key facts

- **NIH application ID:** 10408840
- **Project number:** 5R21AI163595-02
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** Karen Scanlon
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $193,125
- **Award type:** 5
- **Project period:** 2021-05-21 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10408840

## Citation

> US National Institutes of Health, RePORTER application 10408840, IDO promotes severe manifestations of B. pertussis infection in infants (5R21AI163595-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10408840. Licensed CC0.

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