Abstract
The agent of human granulocytic ehrlichiosis (aoHGE) is a tick-borne, obligate intracellular, granulocytotropic bacterium able to infect numerous host species. Given its unique niche and the leukopenia often noted with infection, we investigated the effect of acute aoHGE infection on neutrophil activation by evaluating surface expression of the β2 integrin CD11b/CD18 in a mouse mo0del using FACS analysis. Infection resulted in neutrophil activation with up-regulation of CD11b/CD18 in multiple strains of mice, however, hematologic analysis showed no apparent role for CD11b/CD18 in mediating peripheral leukopenia. Because IFN-γ is an important cytokine during granulocytic ehrlichiosis and is known to activate leukocytes, we investigated the potential role of IFN-γ in CD11b/CD18 up-regulation. Neutrophils from IFN-γ knock-out mice became activated during aoHGE infection, however, the kinetics of activation differed from wild-type mice. In addition, activation correlated directly with the presence of bacteria because neutrophils with large intracytoplasmic morula also expressed higher levels of CD11b/CD18. CD11b/CD18 seemed to be critical to early bacterial clearance and killing in vivo because infection of mice with targeted genetic disruption of CD11b/CD18 resulted in an initial increase in bacterial burden compared with wild-type mice. Similarly, in vitro culture of neutrophils from infected CD11b/CD18 knock-out mice resulted in a marked increase in bacterial proliferation compared with congenic controls. The data support crucial roles of CD11b/CD18 and IFN-γ-mediated cell activation as mechanisms that limit bacterial replication.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 303-311 |
| Number of pages | 9 |
| Journal | Laboratory Investigation |
| Volume | 82 |
| Issue number | 3 |
| State | Published - 2002 |
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ASJC Scopus subject areas
- Pathology and Forensic Medicine
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Kinetics of CD11b/CD18 up-regulation during infection with the agent of human granulocytic ehrlichiosis in mice. / Borjesson, Dori L; Simon, Scott I.; Hodzic, Emir; Ballantyne, Christie M.; Barthold, Stephen W.
In: Laboratory Investigation, Vol. 82, No. 3, 2002, p. 303-311.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Kinetics of CD11b/CD18 up-regulation during infection with the agent of human granulocytic ehrlichiosis in mice
AU - Borjesson, Dori L
AU - Simon, Scott I.
AU - Hodzic, Emir
AU - Ballantyne, Christie M.
AU - Barthold, Stephen W
PY - 2002
Y1 - 2002
N2 - The agent of human granulocytic ehrlichiosis (aoHGE) is a tick-borne, obligate intracellular, granulocytotropic bacterium able to infect numerous host species. Given its unique niche and the leukopenia often noted with infection, we investigated the effect of acute aoHGE infection on neutrophil activation by evaluating surface expression of the β2 integrin CD11b/CD18 in a mouse mo0del using FACS analysis. Infection resulted in neutrophil activation with up-regulation of CD11b/CD18 in multiple strains of mice, however, hematologic analysis showed no apparent role for CD11b/CD18 in mediating peripheral leukopenia. Because IFN-γ is an important cytokine during granulocytic ehrlichiosis and is known to activate leukocytes, we investigated the potential role of IFN-γ in CD11b/CD18 up-regulation. Neutrophils from IFN-γ knock-out mice became activated during aoHGE infection, however, the kinetics of activation differed from wild-type mice. In addition, activation correlated directly with the presence of bacteria because neutrophils with large intracytoplasmic morula also expressed higher levels of CD11b/CD18. CD11b/CD18 seemed to be critical to early bacterial clearance and killing in vivo because infection of mice with targeted genetic disruption of CD11b/CD18 resulted in an initial increase in bacterial burden compared with wild-type mice. Similarly, in vitro culture of neutrophils from infected CD11b/CD18 knock-out mice resulted in a marked increase in bacterial proliferation compared with congenic controls. The data support crucial roles of CD11b/CD18 and IFN-γ-mediated cell activation as mechanisms that limit bacterial replication.
AB - The agent of human granulocytic ehrlichiosis (aoHGE) is a tick-borne, obligate intracellular, granulocytotropic bacterium able to infect numerous host species. Given its unique niche and the leukopenia often noted with infection, we investigated the effect of acute aoHGE infection on neutrophil activation by evaluating surface expression of the β2 integrin CD11b/CD18 in a mouse mo0del using FACS analysis. Infection resulted in neutrophil activation with up-regulation of CD11b/CD18 in multiple strains of mice, however, hematologic analysis showed no apparent role for CD11b/CD18 in mediating peripheral leukopenia. Because IFN-γ is an important cytokine during granulocytic ehrlichiosis and is known to activate leukocytes, we investigated the potential role of IFN-γ in CD11b/CD18 up-regulation. Neutrophils from IFN-γ knock-out mice became activated during aoHGE infection, however, the kinetics of activation differed from wild-type mice. In addition, activation correlated directly with the presence of bacteria because neutrophils with large intracytoplasmic morula also expressed higher levels of CD11b/CD18. CD11b/CD18 seemed to be critical to early bacterial clearance and killing in vivo because infection of mice with targeted genetic disruption of CD11b/CD18 resulted in an initial increase in bacterial burden compared with wild-type mice. Similarly, in vitro culture of neutrophils from infected CD11b/CD18 knock-out mice resulted in a marked increase in bacterial proliferation compared with congenic controls. The data support crucial roles of CD11b/CD18 and IFN-γ-mediated cell activation as mechanisms that limit bacterial replication.
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UR - http://www.scopus.com/inward/citedby.url?scp=0036131113&partnerID=8YFLogxK
M3 - Article
C2 - 11896209
AN - SCOPUS:0036131113
VL - 82
SP - 303
EP - 311
JO - Laboratory Investigation
JF - Laboratory Investigation
SN - 0023-6837
IS - 3
ER -