# NK cell and interferon gamma deficiency in infant susceptibility to pertussis

> **NIH NIH R21** · UNIVERSITY OF MARYLAND BALTIMORE · 2021 · $231,750

## Abstract

PROJECT SUMMARY
 Recent levels of pertussis, caused by the bacterial pathogen Bordetella pertussis, are at their highest
in the U.S. since the 1950s. In typical pertussis disease, respiratory symptoms are followed by episodes of
severe and persistent paroxysmal coughing. In infants, the disease can progress to serious pulmonary
complications, often requiring hospital intensive care, and fatal outcomes are possible. However, we still
have a poor understanding of the pathogenesis of pertussis and there are no consistently effective
therapeutic interventions for infants suffering from this potentially deadly bacterial infection.
 In mouse models of pertussis, several parallels with human pertussis disease reflect the age-
dependent outcomes of infection, such as hyperleukocytosis and organ pathologies seen in infant but not
adult mice. Infant mice suffer a lethal disseminating infection while adult mice restrict infection to the
respiratory tract and recover. A likely contributing factor to the relative susceptibility of infants versus adults
to severe pertussis (and to various other infections) is the different and developing immune system of infants
compared to that of adults. This includes limited Th1-polarizing cytokine responses, primarily interferon
gamma (IFNg), to most stimuli in infants. Interestingly, adult mice lacking either the IFNg receptor (IFNgR) or
natural killer (NK) cells (major early producers of IFNg) fail to restrict B. pertussis infection to the respiratory
tract and suffer a lethal disseminating infection, similar to the infection seen in infant wild type mice. Our
preliminary data indicate poor IFNg responses to B. pertussis infection in infant mice in contrast to robust
IFNg responses in adult mice, a relative deficit of NK cells in the lungs and spleens of infant mice, and poor
expression of cytokines that activate NK cells to produce IFNg. Therefore, we hypothesize that deficient NK
cell and IFNg levels and/or responses in infant mice contribute significantly to their susceptibility to lethal
disseminating B. pertussis infection.
 To test these hypotheses, the aims of this proposal are (i) to investigate the contribution of NK cell
and IFNg deficiencies to the susceptibility of infants to lethal disseminating B. pertussis infection, and (ii) to
determine whether deficiency in production of NK cell-activating cytokines (resulting in lower
IFNg production) in infants is due to deficiency in macrophage activation in response to B. pertussis. We will
use a combination of mouse infection, adoptive cell transfer and cell culture studies to test these hypotheses
and begin to investigate mechanisms, and we will take advantage of genetically altered mice to facilitate
these studies. Identification of host targets for development of novel therapeutics for infants suffering from
debilitating and sometimes fatal pertussis will have a major public health impact on this disease.

## Key facts

- **NIH application ID:** 10108422
- **Project number:** 1R21AI156042-01
- **Recipient organization:** UNIVERSITY OF MARYLAND BALTIMORE
- **Principal Investigator:** NICHOLAS H CARBONETTI
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $231,750
- **Award type:** 1
- **Project period:** 2021-03-11 → 2023-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10108422

## Citation

> US National Institutes of Health, RePORTER application 10108422, NK cell and interferon gamma deficiency in infant susceptibility to pertussis (1R21AI156042-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10108422. Licensed CC0.

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