TY - JOUR
T1 - Impaired bactericidal but not fungicidal activity of polymorphonuclear neutrophils in patients with chronic lymphocytic leukemia
AU - Kontoyiannis, Dimitrios P.
AU - Georgiadou, Sarah P.
AU - Wierda, William G.
AU - Wright, Susan
AU - Albert, Nathaniel D.
AU - Ferrajoli, Alessandra
AU - Keating, Michael
AU - Lewis, Russell E.
N1 - Funding Information:
This study was supported by a grant from the CLL Global Research Foundation (to D.P.K.). This research is supported in part by the National Institutes of Health through M. D. Anderson ’s Cancer Center Support Grant CA016672.
PY - 2013/8
Y1 - 2013/8
N2 - We examined the qualitative polymorphonuclear neutrophil (PMN)-associated immune impairment in patients with chronic lymphocytic leukemia (CLL) by characterizing phagocytic killing of key non-opsonized bacterial (Staphylococcus aureus and Pseudomonas aeruginosa) and fungal (Candida albicans and Aspergillus fumigatus) pathogens. Neutrophils were collected from 47 non-neutropenic patients with CLL (PMN count > 1000/mm3) and age-matched and young healthy controls (five each). A subset of patients (13%) had prior or subsequent infections. We found that the patients with CLL had diminished PMN microbicidal response against bacteria but not against fungi compared with the controls. Compared to patients with effective PMN responses, we did not identify differences of basal PMN pathogen-associated molecular pattern receptor gene expression, soluble pathogen-associated molecular pattern gene expression or inflammatory cytokine signatures in patients with impaired PMN responses when PMNs were analyzed in multiplex real-time polymerase chain reaction assays. However, differences in PMN microbicidal response against A. fumigatus in patients with CLL were associated with the degree of hypogammaglobulinemia.
AB - We examined the qualitative polymorphonuclear neutrophil (PMN)-associated immune impairment in patients with chronic lymphocytic leukemia (CLL) by characterizing phagocytic killing of key non-opsonized bacterial (Staphylococcus aureus and Pseudomonas aeruginosa) and fungal (Candida albicans and Aspergillus fumigatus) pathogens. Neutrophils were collected from 47 non-neutropenic patients with CLL (PMN count > 1000/mm3) and age-matched and young healthy controls (five each). A subset of patients (13%) had prior or subsequent infections. We found that the patients with CLL had diminished PMN microbicidal response against bacteria but not against fungi compared with the controls. Compared to patients with effective PMN responses, we did not identify differences of basal PMN pathogen-associated molecular pattern receptor gene expression, soluble pathogen-associated molecular pattern gene expression or inflammatory cytokine signatures in patients with impaired PMN responses when PMNs were analyzed in multiplex real-time polymerase chain reaction assays. However, differences in PMN microbicidal response against A. fumigatus in patients with CLL were associated with the degree of hypogammaglobulinemia.
KW - Aspergillus fumigatus
KW - CLL
KW - Candida albicans
KW - Infection
KW - Innate immunity
KW - Neutrophil function
KW - Pseudomonas aeruginosa
KW - Staphylococcus aureus
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U2 - 10.3109/10428194.2012.750723
DO - 10.3109/10428194.2012.750723
M3 - Article
C2 - 23163595
AN - SCOPUS:84880315137
SN - 1042-8194
VL - 54
SP - 1730
EP - 1733
JO - Leukemia and Lymphoma
JF - Leukemia and Lymphoma
IS - 8
ER -