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Principal Investigator: Shaunna Simmons
Organization: STATE UNIVERSITY OF NEW YORK AT BUFFALO
Fiscal Year: 2024
Award: $34,599
Funding agency: National Institute of Allergy and Infectious Diseases
Streptococcus pneumoniae (pneumococcus) are Gram-positive bacteria responsible for 1.6 million deaths
globally each year. Available pneumococcal vaccines have reduced efficacy in the elderly, and despite
vaccination, S. pneumoniae remain the leading cause of bacterial community-acquired pneumonia in adults over
the age of 65. This decline in vaccine efficacy is driven by immunosenescence, the age-associated decline in
immune function. Polymorphonuclear leukocytes (PMNs) are cells of the innate immune system and are required
for host defense against S. pneumoniae infection. PMNs isolated from aged hosts display a significant reduction
in pneumococcal killing when compared to PMNs from young hosts. This reduction in killing persists despite
opsonization of bacteria with specific anti-pneumococcal antibodies, however, the signaling pathways driving
this decline in PMN function and the role of PMNs in the age-related reduction in vaccine efficacy remain unclear.
One pathway that controls PMN antibacterial responses is the extracellular adenosine pathway but the role of
this pathway in vaccinated hosts and how it changes with age remain unexplored. This led to the hypothesis
that with age, there is a decline in intracellular bacterial killing following antibody mediated uptake of S.
pneumoniae, which is driven by changes in adenosine receptor signaling. This hypothesis will be tested using
two specific aims: 1) Identify why intracellular killing of S. pneumoniae is defective in PMNs from old mice and
2) Identify the role of adenosine receptor signaling in the age-driven decline in intracellular killing of S.
pneumoniae by PMNs. This project is significant as it will identify the mechanism of the age-related changes in
PMN function following antibody mediated uptake of S. pneumoniae. Additionally, PMNs are involved in host
defense against multiple pathogens, therefore this work may provide a potential therapeutic target to boost
overall vaccine protectiveness in aged hosts. The overall goal of this research training plan is to strengthen the
candidate’s knowledge in host-pathogen interactions, immunology, and immunosenescence. As well as to
advance technical skills in microscopy, signaling, and cell biology techniques. These aims and goals will be
accomplished with the guidance of the qualified mentoring team assembled by the candidate and will be aided
by the opportunities offered by the training environment at the University at Buffalo Jacobs School of Medicine
and Biomedical Sciences. These resources will provide the necessary training and support to complete the
proposed research and guide the candidate’s future career in academia.
Terms: <21+ years old><65 and older><65 or older><65 years of age and older><65 years of age or more><65 years of age or older><65+ years><65+ years old><> 65 years><Academia><Adenosine><Adenosine A1 Receptor><Adenosine Receptors><Adult><Adult Human><Affect><Age><Aged 65 and Over><Aging><Anti-Bacterial Agents><Anti-Bacterial Response><Antibacterial Response><Antibodies><Antisera><Bacteria><Blood Neutrophil><Blood Polymorphonuclear Neutrophil><Cell Body><Cell Communication and Signaling><Cell Signaling><Cell surface><Cells><Cellular Immune Function><Cellular biology><Cellular injury><Cessation of life><Complement><Complement Proteins><Complement Receptor><Cytoplasmic Granules><D pneumoniae><D. pneumoniae><Data><Death><Defect><Deposit><Deposition><Diplococcus pneumoniae><ERK 1><ERK1><ERK1 Kinase><Elderly><Environment><Exposure to><Extracellular Signal-Regulated Kinase 1><Extracellular Signal-Regulated Kinase Gene><Fc Receptor><Future><Goals><Gram-Positive Bacteria><Host Defense><Host resistance><Human><Immune><Immune Sera><Immune response><Immunes><Immunize><Immunological response><Immunology><Impairment><Infection><Innate Immune System><Intracellular Communication and Signaling><Knowledge><MAP Kinase 3><MAP Kinase Gene><MAPK><MAPK3><MAPK3 Mitogen-Activated Protein Kinase><MAPK3 gene><Marrow Neutrophil><Mediating><Mentors><Mice><Mice Mammals><Microscopy><Mitogen-Activated Protein Kinase 3><Mitogen-Activated Protein Kinase 3 Gene><Mitogen-Activated Protein Kinase Gene><Modern Man><Murine><Mus><Neutrophilic Granulocyte><Neutrophilic Leukocyte><Opsonin><P1 Purinoceptors><P44ERK1><PSTkinase p44mpk><Pathway interactions><Phagocytosis><Phagosomes><Pneumococcal Infections><Pneumococcal conjugate vaccine><Pneumococcal vaccine><Pneumococcus><Polymorphonuclear Cell><Polymorphonuclear Leukocytes><Polymorphonuclear Neutrophils><Predisposition><Prevenar><Prevnar><Production><Purinergic P1 Receptors><Qualifying><RNA Seq><RNA sequencing><RNAseq><Receptor Protein><Receptor Signaling><Research><Research Resources><Research Training><Resistance><Resources><Role><S pneumoniae><S. pneumoniae><Science><Signal Pathway><Signal Transduction><Signal Transduction Systems><Signaling><Streptococcus pneumoniae><Streptococcus pneumoniae Infections><Streptococcus pneumoniae vaccine><Surface><Susceptibility><Technical Expertise><Techniques><Testing><Time><Training><Universities><Vaccinated><Vaccination><Vaccines><Vulnerable Populations><Work><above age 65><adulthood><advanced age><after age 65><age 65 and greater><age 65 and older><age 65 or older><age > 65><age associated><age associated alterations><age associated changes><age associated decline><age correlated><age correlated alterations><age correlated changes><age dependent><age dependent alterations><age dependent changes><age dependent decline><age linked><age of 65 years onward><age related><age related alterations><age related changes><age related decline><age specific><age specific alterations><age specific changes><aged><aged 65 and greater><aged 65+><aged mice><aged mouse><aged ≥65><ages><alterations with age><anti-bacterial><anti-microbial><antibody receptor><antimicrobial><bacterial community><bactericidal><bactericide><biological signal transduction><booster dose><booster shot><booster vaccine><career><cell biology><cell damage><cell injury><cellular damage><changes with age><community acquired pneumonia><community associated pneumonia><complementation><damage to cells><decline with age><design><designing><elderly mice><extracellular><geriatric><granule><host response><human old age (65+)><immune function><immune senescence><immune serum><immune system function><immune system response><immunoresponse><immunosenescence><improved><injury to cells><medical college><medical schools><neutrophil><old age><old mice><over 65 years><p44 MAPK><pathogen><pathway><pneumococcal disease><pneumococcus infection><receptor><recruit><resistant><response><school of medicine><senior citizen><social role><technical skills><therapeutic target><transcriptome sequencing><transcriptomic sequencing><uptake><vaccine boost><vaccine efficacy><vulnerable group><vulnerable individual><vulnerable people><≥65 years>