Pneumonia remains the #1 killer of children in the world and is a leading cause of morbidity and mortality in children in the US and the #8 cause of mortality in adults. Our laboratory has made seminal insights in mechanisms underlying host defense against extracelluar pathogens ? particularly in the area of type 17 cytokines ?IL-17 and IL-22. We have identified novel pathways that regulate host immunity against Pneumocystis including CD4+ T-cell intrinsic IL21R expression and STAT3 activation. We will determine how CD4+ T-cell STAT3 regulates host resistance and test the specific roles of IL-22, GM-CSF and CD209 isoforms. Furthermore we will examine the role of IL-22RA2 in regulating the availability of free IL-22 in the lung and study the contributions of tissue resident memory cells in host defense against bacterial pneumonia. The research prosed under this R35 will shed new light on pulmonary host defenses that can be exploited to reduce the global burden of pneumonia mortality and morbidity.

Public Health Relevance

Pneumonia remains the #1 killer of children in the world and is a leading cause of morbidity and mortality in children in the US and the #8 cause of mortality in adults. This proposal will conduct research to better understand host resistance against pneumonia that can be used to develop new therapies or vaccines to prevent or treat pneumonia.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Unknown (R35)
Project #
5R35HL139930-03
Application #
9853049
Study Section
Special Emphasis Panel (ZHL1)
Program Officer
Craig, Matt
Project Start
2018-02-01
Project End
2025-01-31
Budget Start
2020-02-01
Budget End
2021-01-31
Support Year
3
Fiscal Year
2020
Total Cost
Indirect Cost
Name
Tulane University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
053785812
City
New Orleans
State
LA
Country
United States
Zip Code
70118
Elsegeiny, Waleed; Zheng, Mingquan; Eddens, Taylor et al. (2018) Murine models of Pneumocystis infection recapitulate human primary immune disorders. JCI Insight 3: