This proposal focuses on the earliest interactions of the F. tularensis the causative agent of tularemia with the host. Our hypothesis is that infection of particular cells in the lung results in a different pattern of host derived immunomodulatory molecules produced that shape the host innate and adaptive immune responses to benefit the pathogen. In this study we will identify the early cells infected in lung and skin infections. We will determine the molecules produced in the earliest cells following infection using a combination of fluorescence activated cell sorting and marked bacteria. By cell purification and in vitro infection we will learn how the impact the subsequent immune response. We will then determine the F. tularensis genes responsible, and their interactions with the host. Finally, we will determine mechanism for immune modulation.
The interaction between hosts and microbes is a complex one with signals going from the microbe to the host and vice versa. In this proposal we investigate how the bacterium that causes tularemia manages to end different signal to the host depending on where the initial infection occurs. We will identify the first cells nfected by the bacteria and how they respond depending on whether infection happens in the lungs or the skin. We will then determine how these cell influence the outcome of the immune response to the bacterium, and which bacteria genes are required. This will allow us to define targets for intervention by drugs.
|Ashbrook, Alison W; Lentscher, Anthony J; Zamora, Paula F et al. (2016) Antagonism of the Sodium-Potassium ATPase Impairs Chikungunya Virus Infection. MBio 7:|
|Bowles, R D; Karikari, I O; VanDerwerken, D N et al. (2016) In vivo luminescent imaging of NF-ÎºB activity and NF-ÎºB-related serum cytokine levels predict pain sensitivities in a rodent model of peripheral neuropathy. Eur J Pain 20:365-76|
|Alayli, Farah; Scholle, Frank (2016) Dengue virus NS1 enhances viral replication and pro-inflammatory cytokine production in human dendritic cells. Virology 496:227-36|
|Bates, John T; Pickens, Jennifer A; Schuster, Jennifer E et al. (2016) Immunogenicity and efficacy of alphavirus-derived replicon vaccines for respiratory syncytial virus and human metapneumovirus in nonhuman primates. Vaccine 34:950-6|
|Fibriansah, Guntur; Tan, Joanne L; Smith, Scott A et al. (2015) A highly potent human antibody neutralizes dengue virus serotype 3 by binding across three surface proteins. Nat Commun 6:6341|
|de St Maurice, Annabelle; Grijalva, Carlos G; Fonnesbeck, Christopher et al. (2015) Racial and Regional Differences in Rates of Invasive Pneumococcal Disease. Pediatrics 136:e1186-94|
|Roberts, Lydia M; Ledvina, Hannah E; Tuladhar, Shraddha et al. (2015) Depletion of alveolar macrophages in CD11c diphtheria toxin receptor mice produces an inflammatory response. Immun Inflamm Dis 3:71-81|
|Smith, Scott A; Silva, Laurie A; Fox, Julie M et al. (2015) Isolation and Characterization of Broad and Ultrapotent Human Monoclonal Antibodies with Therapeutic Activity against Chikungunya Virus. Cell Host Microbe 18:86-95|
|Pulendran, Bali (2015) The varieties of immunological experience: of pathogens, stress, and dendritic cells. Annu Rev Immunol 33:563-606|
|Price, Aryn A; Sampson, Timothy R; Ratner, Hannah K et al. (2015) Cas9-mediated targeting of viral RNA in eukaryotic cells. Proc Natl Acad Sci U S A 112:6164-9|
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