Infection-induced modulation of m1 and m2 phenotypes in circulating monocytes: role in immune monitoring and early prognosis of sepsis.
To monitor and better understand the immunoinflammatory sequelae in sepsis and septic shock, systemic and monocyte-related cytokine responses were evaluated in baboons with experimental peritonitis induced by an E. coli-laden fibrin clot. Despite similar bacterial inocula, considerable interindividual variability in clinical manifestation and outcome of infection was observed. Because monocytes and macrophages are a key component of innate immunity, we hypothesized that early polarization of distinct activation programs in circulating monocytes that culminates in the emergence of either classically (M1) or alternatively (M2) activated monocytes may underlie the observed susceptibility or resistance to infection. To test our hypothesis, we analyzed infection-induced expression of cytokine mRNAs in monocytes isolated from surviving and dead animals. Our data show that resistance to E. coli sepsis may well be associated with a mixed M1/M2 activation state of circulating monocytes, whereas M1 phenotype appeared to be prevailing in monocytes from animals that died. Together with data on systemic cytokine responses, the latter findings indicate that morbidity and mortality of animals with gram-negative sepsis may well result from an overwhelming proinflammatory response. Collectively, our data contribute to a better understanding of cytokine networking in the immunoinflammatory response to microbial infection and suggest M1/M2 immunophenotypic profiling of readily available circulatory monocytes for early prognosis of severe infections.
Department of Basic Medical Science, University of Missouri, School of Medicine, Kansas City, Missouri, USA.
Ashish
A
Mehta
Ryan
R
Brewington
Manjil
M
Chatterji
Mikhail
M
Zoubine
Gary T
GT
Kinasewitz
Glenn T
GT
Peer
Alvin C K
AC
Chang
Fletcher B
FB
Taylor
Alex
A
Shnyra
D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004731:Endotoxins / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D005337:Fibrin / Q000737:chemistry; D007249:Inflammation; D007963:Leukocytes, Mononuclear / Q000166:cytology; D051379:Mice; D009000:Monocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D010215:Papio; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011379:Prognosis; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018805:Sepsis / Q000097:blood* / Q000175:diagnosis* / Q000473:pathology; D013997:Time Factors
D016207:Cytokines; D017931:DNA Primers; D004731:Endotoxins; D012333:RNA, Messenger; D012313:RNA; D005337:Fibrin