Richard Davis

Advisor
Neutrophil Responses to Infection with Leishmania Parasites: MHC Class II-expression and Parasite Life-stage Interactions
Biography

My dissertation research has focused on immune responses during leishmaniasis, the disease caused by the protozoan parasites of the genus Leishmania. I am particularly interested in the influence of the early innate immune response in shaping the induction of long-term adaptive immune response and, conversely, how parasites are able to change or exploit innate immune cells during the establishment of chronic disease. Specifically, I have examined changes in global neutrophil and immune-cell populations during Leishmania infection in both murine and human models of leishmaniasis. Working together with collaborating investigators in Brazil (Federal University of Bahia), I was able to travel to Brazil and, in a rural leishmaniasis-treatment clinic, examine peripheral blood immune cells from patients. This research resulted in the novel finding that, in a subset of patients, neutrophils began to express characteristics and functions similar to professional antigen-presenting molecules like dendritic cells. Specifically we found that a subset of patient neutrophils expressed the antigen-presenting molecule MHC Class II (known as HLA-DR in humans). Furthermore, these MHCII+ neutrophils showed increase surface expression of costimulatory molecules but also increased markers of neutrophil activation and degranulation. Furthermore, using murine models of acute and chronic Leishmania infection I was able to identify and isolate MHCII-expressing neutrophils capable of influencing T cell responses in vitro. Overall, these findings suggest the existence of a unique subset of neutrophils that are perhaps similar to a recently described population of neutrophil-dendritic cell hybrids. The results of this project have provided valuable insight into mechanisms of parasite-host interactions and determined a potentially novel role for innate immune cells.

Davis RE, Sharma S, Conceição J, Carneiro P, Novais F, Scott P, Sundar S, Bacellar O, Carvalho EM, Wilson ME. Phenotypic and functional characteristics of HLA-DR(+) neutrophils in Brazilians with cutaneous leishmaniasis. J Leukoc Biol. 2017 Mar;101(3):739-749. doi: 10.1189/jlb.4A0915-442RR. PubMed PMID: 28076241;PubMed Central PMCID: PMC5295851.

Clay GM, Valadares DG, Graff JW, Ulland TK, Davis RE, Scorza BM, Zhanbolat BS, Chen Y, Sutterwala FS, Wilson ME. An Anti-Inflammatory Role for NLRP10 in Murine Cutaneous Leishmaniasis. J Immunol. 2017 Oct 15;199(8):2823-2833. doi:10.4049/jimmunol.1500832. Epub 2017 Sep 20. PubMed PMID: 28931602; PubMed Central PMCID: PMC5679237.

Sharma S, Davis RE, Srivastva S, Nylén S, Sundar S, Wilson ME. A Subset of Neutrophils Expressing Markers of Antigen-Presenting Cells in Human Visceral Leishmaniasis. J Infect Dis. 2016 Nov 15;214(10):1531-1538. PubMed PMID:27601622; PubMed Central PMCID: PMC5091370.

Conceição J, Davis R, Carneiro PP, Giudice A, Muniz AC, Wilson ME, Carvalho EM, Bacellar O. Characterization of Neutrophil Function in Human Cutaneous Leishmaniasis Caused by Leishmania braziliensis. PLoS Negl Trop Dis. 2016 May 11;10(5):e0004715. doi: 10.1371/journal.pntd.0004715. PubMed PMID: 27167379;PubMed Central PMCID: PMC4864077.

Davis R, Flanigan T, Wilson E. Passive gravitational sedimentation ofperipheral blood increases the sensitivity of microscopic detection of malaria. Asian Pac J Trop Med. 2013 Jul;6(7):552-5. doi: 10.1016/S1995-7645(13)60095-4. PubMed PMID: 23768828.

Honors and Awards

  • Immunology Predoctoral Training Grant 2010-11 and 2012-14
  • Stanley Graduate Award for International Research, 2013
  • First Place Presidential Award, Society for Leukocyte Biology, Society for Leukocyte Biology/International Endotoxin and Innate Immunity Joint Conference, Salt Lake City, UT (2014)
  • First Place-Oral Presentation, Great Plains Emerging Infectious Diseases Conference, Iowa City, IA (2014)
  • ECGPS Research Award, University of Iowa, Iowa City, IA (2013)
Director
Clinical Microbiology
Providence Sared Heart Medical Center and Children's Hospital
Richard Davis