Monocytes provide defense against infection and serve as progenitors for tissue macrophages and dendritic cells. Recruitment of monocytes to sites of infection begins with trafflcl Our first aim i s to investigate Ly6Chi monocyte reconstitution and the localization and responsiveness of monocytes and MSCs following allo-HSCT. We will use CCR2 and MCP-1 reporter mice to investigate monocytes following allo-HSCT. We will use a conditional MCP-1 knockout mouse strain to determine the contribution of MSCs to the development ofthe inflammatory monocyte compartment.
Our second aim i s to determine the Impact of GvHD on monocyte trafficking and to determine the role of Ly6Chi monocytes in the development of GvHD. We will aiso quantify inflammatory monocyte numbers in patients following allo-HSCT and correlate circulating monocyte levels with subsequent development of GvHD.
Our third aim addresses our hypothesis that changes in the intestinal microbota following allo-HSCT influence monocyte emigration from bone marrow. We will investigate changes in the intestinal microbiota during allo- HSCT using high-throughput 16S rDNA sequencing and correlate changes in the intestinal microbiota with circulating inflammatory monocyte levels and activation. The studies described in this project will identify in vivo mechanisms that drive reconstitution ofthe monocyte compartment and will define the role of the intestinal microbiota in re-establishing immune homeostasis following allo-HSCT.

Public Health Relevance

Monocytes are a subset of blood cells that move from the bone marrow to tissues, where they can fight infections. The experiments we are proposing will determine which factors following bone marrow transplantation are important for optimal reconstitution of monocytes. These studies may lead to new approaches to minimize infections and graft versus host disease following transplantation.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA023766-35
Application #
8739761
Study Section
Special Emphasis Panel (ZCA1)
Project Start
Project End
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
35
Fiscal Year
2014
Total Cost
Indirect Cost
City
New York
State
NY
Country
United States
Zip Code
Staffas, Anna; Burgos da Silva, Marina; Slingerland, Ann E et al. (2018) Nutritional Support from the Intestinal Microbiota Improves Hematopoietic Reconstitution after Bone Marrow Transplantation in Mice. Cell Host Microbe 23:447-457.e4
Velardi, Enrico; Tsai, Jennifer J; Radtke, Stefan et al. (2018) Suppression of luteinizing hormone enhances HSC recovery after hematopoietic injury. Nat Med 24:239-246
Moskowitz, Craig H (2018) Should all patients with HL who relapse after ASCT be considered for allogeneic SCT? A consult, yes; a transplant, not necessarily. Blood Adv 2:821-824
Kim, Seong Jin; Huang, Yao-Ting; Foldi, Julia et al. (2018) Cytomegalovirus resistance in CD34+ -selected hematopoietic cell transplant recipients. Transpl Infect Dis 20:e12881
Maslak, Peter G; Dao, Tao; Bernal, Yvette et al. (2018) Phase 2 trial of a multivalent WT1 peptide vaccine (galinpepimut-S) in acute myeloid leukemia. Blood Adv 2:224-234
DeFilipp, Zachariah; Peled, Jonathan U; Li, Shuli et al. (2018) Third-party fecal microbiota transplantation following allo-HCT reconstitutes microbiome diversity. Blood Adv 2:745-753
Haak, Bastiaan W; Littmann, Eric R; Chaubard, Jean-Luc et al. (2018) Impact of gut colonization with butyrate-producing microbiota on respiratory viral infection following allo-HCT. Blood 131:2978-2986
Boudreau, Jeanette E; Hsu, Katharine C (2018) Natural Killer Cell Education and the Response to Infection and Cancer Therapy: Stay Tuned. Trends Immunol 39:222-239
Lin, Richard J; Ho, Caleb; Hilden, Patrick D et al. (2018) Allogeneic haematopoietic cell transplantation impacts on outcomes of mantle cell lymphoma with TP53 alterations. Br J Haematol :
Malard, Florent; Labopin, Myriam; Cho, Christina et al. (2018) Ex vivo and in vivo T cell-depleted allogeneic stem cell transplantation in patients with acute myeloid leukemia in first complete remission resulted in similar overall survival: on behalf of the ALWP of the EBMT and the MSKCC. J Hematol Oncol 11:127

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