Immunological damage effects of cytomegalovirus infection on bone marrow hematopoietic cells

Abstract

Objective: Toobserve the damage effects of cytomegalovirus (CMV) infection on hematopoietic cells and to investigate the clinical significance. Methods: (1) ELISA assay wasused to detect IL-17 and IFN-γ levels in the peripheral blood serum of 36 patients on pretherapy and posttherapy. (2) Changes of peripheral blood lymphocyte subsets were detected by FACS. (3) Cytological observation of cervical lymph nodes was executed by needle aspiration cytology. (4) Cellular immunochemistry and immunofluorescence staining were performed to observe the POX release, HLA-DR expression, IL-17A and IFN-γ secretion-like expression status of activated immune cells in the bone marrow hematopoietic microenvironment. Serum samples from healthy individuals were used as controls. Bone marrow smears from patients without iron deficiency anemia were compared as bone marrow immunostaining. Results: (1) Serum levels of IL-17 and IFN-γ were significantly increased in CMV-infected patients [IL-17 (48.23±3.86) ng/L vs (20.16±1.05) ng/L,respectively; IFN-γ (40.16±3.11) vs (8.17±1.92) ng/L,P<0.01]. (2) The proportion of CD16+/CD56+NK cells was significantly increased in patients [(43.54±6.01)% vs (14.01±3.25)%, P<0.01]. The proportion of CD3+CD4+T and CD3+CD8+T cells decreased,(20.91±53.15)% vs (35.10±4.88)%, and (15.41±5.13)% vs (25.11±3.92)%,respectively,P<0.05. (3) Large numbers of abnormal lymphocytes and macrophages (MΦ) that engulf large quantities of CMV inclusion bodies were observed in bone marrow and lymph nodes. CMV infected and destroied the hematopoietic cells of various lines in the bone marrow. The activated MΦ phagocytizedthe CMV inclusion bodies and also phagocytosed CMV-infected blood cells. (4) Activated MΦ in bone marrow hematopoietic microenvironment released POX strongly positive, highly expressed class Ⅱ HLA-DR, and highly expressed inflammatory factors IL-17A and IFN-γ. (5) Twenty-twopatients with elevated WBC were treated with ganciclovir combined with antibiotics for 2 weeks after the disappearance of the foci, WBC counts and CMV-IgM levels of 16 cases were reduced to normal.Six patients with CMV who were not turned negative were tprolonged,and the granulocyte and/or platelet counts fell below normal range. Fourteenpatients withreduced granulocyte or platelet count, CMV-IgM levels were slow descend,and the ganciclovir treated more than 4 weeks. Conclusions: CMV can infect hematopoietic bone marrow nucleated blood cells and destroy hematopoiesis. NK and MΦ cells are important effector cells against CMV infection. Activated macrophages are dual in nature, they can engulf CMV virus and virus-infected blood cells,and also aggravate bone marrow immune damage by releasing inflammatory factors such as POX and IL-17A and IFN-γ.