eprintid: 35975
rev_number: 39
userid: 6982
dir: disk0/00/03/59/75
datestamp: 2019-06-20 21:38:21
lastmod: 2019-09-05 12:43:29
status_changed: 2019-06-20 21:38:21
type: thesis_degree
metadata_visibility: show
contact_email: justin.s.dutta@gmail.com
item_issues_id: etd_invalid_date_35975
item_issues_id: duplicate_title_29903
item_issues_id: similar_title_36201
item_issues_type: etd_invalid_date
item_issues_type: duplicate_title
item_issues_type: similar_title
item_issues_description: ETD - Invalid Date for Defense Date '2019-04'.  Date must contain Year, Month and Day values.
item_issues_description: Duplicate title to 


    <span class="person_name">test, test</span>
  



<a href="http://d-scholarship.pitt.edu/cgi/users/home?screen=EPrint::View&amp;eprintid=29903"><xhtml:em xmlns:xhtml="http://www.w3.org/1999/xhtml">test.</xhtml:em></a>


    Doctoral Dissertation, University of Pittsburgh.
  


   (Unpublished)
item_issues_description: Similar title to 


    <span class="person_name">Mody, Dillon</span>
  

(2019)

<a href="http://d-scholarship.pitt.edu/cgi/users/home?screen=EPrint::View&amp;eprintid=36201"><xhtml:em xmlns:xhtml="http://www.w3.org/1999/xhtml">Test.</xhtml:em></a>


    Master Essay, University of Pittsburgh.
item_issues_timestamp: 2019-04-23 06:02:12
item_issues_timestamp: 2019-04-23 06:02:12
item_issues_timestamp: 2019-04-23 06:02:12
item_issues_status: autoresolved
item_issues_status: autoresolved
item_issues_status: autoresolved
item_issues_count: 0
eprint_status: archive
creators_name: Dutta, Justin
creators_email: j.dutta@pitt.edu
creators_id: jsd30
creators_orcid: 0000-0002-1740-0639
title: Follistatin-like protein 1 deficiency confers protection from Klebsiella pneumoniae pulmonary infection
ispublished: unpub
divisions: sch_gsph_infectiousdiseasesmicrobiology
full_text_status: restricted
keywords: Follistatin-like protein
abstract: Klebsiella pneumoniae is the third most common cause of nosocomial infections and leads to tremendous burden on health care spending and infection control, due to multiple drug resistance to the majority of present-day antibiotics.  Elucidating the role of diverse innate immunity control mechanisms and signaling pathways in Klebsiella pneumoniae host response is essential in public health importance for developing new therapeutic antibiotic-alternatives.  There is currently a gap in the research literature about the role of Follistatin-like protein 1 in infectious diseases.  In this study, we establish that innate mechanisms can play a protective role in a Klebsiella pneumoniae pulmonary infection murine model via decreased secreted glycoprotein Follistatin-Like 1 Protein (FSTL1).  Using a FSTL1 hypomorphic in vivo mouse model, we discovered that deficiency in FSTL1 production leads to significantly lower Klebsiella pneumoniae infectious burden (p<0.005) in a  lung infection model.  We additionally assessed gene expression by real-time qPCR that this lower burden was associated with differences in pro-inflammatory cytokine signaling, as expression of il7a, il1b, and csf3 were all significantly upregulated in FSTL1 hypomorphic mice compared to C57B6 wildtype controls.  We further identified that FSTL1 hypomorphic mice express significantly higher γδ T cell receptor components, trdc (p<0.001) and trv4 (p<0.005), as well as increased populations of γδ T cells with significantly higher in IL-17A cytokine production (p<0.05) via flow cytometry analysis.  These phenotypes were not able to be phenocopied in FSTL1 conditional knockout mice or the FSTL1 neutralizing antibody experimental model, suggesting that FSTL-1 hypomorph mice, uniquely, have increased γδ T-cells populations that likely are essential for control of infection.  Our study provides evidence that deficient FSTL1 production in genetic and developmental mouse model can protect against Klebsiella pneumoniae lung infection. If this discovery is translational to the human condition, it could signify further research into FSTL1 protein as a host-oriented broad-spectrum drug target is warranted.
date: 2019-06-20
date_type: published
pages: 48
institution: University of Pittsburgh
refereed: TRUE
centers: cen_other_biologicimaging
etdcommittee_type: committee_chair
etdcommittee_type: committee_member
etdcommittee_type: committee_member
etdcommittee_name: Mattila, Joshua
etdcommittee_name: Campfield, Brian
etdcommittee_name: Finegold, David
etdcommittee_email: jmattila@pitt.edu
etdcommittee_email: Brian.Campfield@chp.edu
etdcommittee_email: dnf@pitt.edu
etd_defense_date: 2019-04-24
etd_approval_date: 2019-06-20
etd_submission_date: 2019-04-22
etd_release_date: 2019-06-20
etd_access_restriction: 3_year
etd_patent_pending: FALSE
thesis_type: thesis
degree: MPH
citation:   Dutta, Justin  (2019) Follistatin-like protein 1 deficiency confers protection from Klebsiella pneumoniae pulmonary infection.  Master's Thesis, University of Pittsburgh.    (Unpublished)  
document_url: http://d-scholarship-dev.library.pitt.edu/35975/7/DuttaJustin_MPHthesis_4_2019.pdf