Investigating long-term immune dysfunction following exposure to perinatal inflammation
Active Project Grant Awarded Last action
- Award ID
- F30AI188816
- Recipient
-
The University Of Iowa UEI Z1H9VJS8NG16
- Awarding agency
-
National Institute of Allergy and Infectious Diseases
National Institutes of Health, Department of Health and Human Services
- Obligated
- $86,424
Award facts
- Assistance listing
- 93.855 Allergy and Infectious Diseases Research
- Completion date 4% complete
- Originally
- Place of performance
- Iowa City, IA 52242, USA
Award details come from USAspending.gov.
Description
- Abstract
- Chorioamnionitis is infection and/or inflammation of the fetal membranes and the placenta and is one of the most common complications during pregnancy. Chorioamnionitis is an independent risk factor for several IM- mune-mediated morbidities, including neonatal sepsis, chronic lung disease of prematurity, and asthma devel- opment in childhood. Although the risks associated with chorioamnionitis are severe, our understanding of the impact of this perinatal inflammatory exposure on offspring immune cell function remains incomplete. Current treatment approaches for chorioamnionitis are non-specific, including broad spectrum antibiotics and supportive care, which may independently increase the risk of asthma development. Therefore, there is a critical need to identify new therapeutic targets that address the underlying immune alterations that occur during chorioamni- onitis. This proposal investigates the central hypothesis that fetal interleukin (IL)-1 receptor (IL-1R) signaling drives chorioamnionitis-induced bacterial tolerance in neonatal offspring by upregulating the toll-like receptor (TLR) regulator tollip. This hypothesis is supported by published data demonstrating that chorioamnionitis is dependent on IL-1 and that chorioamnionitis results in post-birth neonatal hyporesponsiveness to bacteria in animals and in humans. My robust preliminary data demonstrates that murine chorioamnionitis-exposed neona- TAL offspring have hyporesponsive splenic macrophages, decreased systemic inflammation, and decreased MOR- tality during neonatal E. Coli sepsis. Additionally, murine chorioamnionitis-exposed neonatal macrophages DIS- play increased chromatin accessibility at the promoter of tollip, which is associated with increased gene expres- sion. The overall objective of my proposal is to determine how chorioamnionitis impacts offspring innate IM- mune function and leads to an increased risk of immune-mediated morbidities. I will address this objective through two specific aims that test 1) the role of IL-1R signaling and 2) the role of tollip in chorioamnionitis- associated neonatal hyporesponsiveness. Upon completion of this project, the expected outcome is that the mechanism(S) underlying chorioamnionitis-induced alterations in macrophage antibacterial responses will be better understood. The broader impact is that this project has the potential to alter current clinical practice by informing therapeutic and preventative approaches for chorioamnionitis that will address the underlying inflam- matory insult.
Transactions
| Action | Obligated | Date |
|---|---|---|
| Amendment | $43,212 | |
| Amendment | $0 | |
| Original award | $43,212 |
Quick answers
Who received award F30AI188816?
F30AI188816 was awarded to The University Of Iowa by National Institute of Allergy and Infectious Diseases (National Institutes of Health) on October 8, 2026.
How much is award F30AI188816 worth?
$86,424 has been obligated on F30AI188816.
On GovTribe
See this award's full record
- Every transaction and subaward
- The recipient's other awards and teaming partners
- Similar grant awards
- Ask GovTribe AI about this award