Host Resistance of CD18 Knockout Mice against Systemic Infection withListeria monocytogenes

Abstract

Mice with targeted mutations of CD18, the common ␤2 subunit of CD11/CD18 integrins, have leukocytosis, impaired transendothelial neutrophil emigration, and reduced host defense to Streptococcus pneumoniae, a gram-positive extracellular bacterium. Previous studies using blocking monoclonal antibodies suggested roles for CD18 and CD11b in hepatic neutrophil recruitment and host innate response to Listeria monocytogenes, a gram-positive intracellular bacterium. We induced systemic listeriosis in CD18 knockout (CD18-ko) and wild-type (WT) mice by tail vein injection with Listeria. By 14 days postinjection (dpi), 8 of 10 WT mice died, compared with 2 of 10 CD18-ko mice (P < 0.01). Quantitative organ culture showed that numbers of Listeria organisms in livers and spleens were similar in both groups at 20 min postinfection. By 3, 5, and 7 dpi, however, numbers of Listeria organisms were significantly lower in livers and spleens of CD18-ko mice than in WT mice. Histopathology showed that following Listeria infection, CD18-ko mice had milder inflammatory and necrotizing lesions in both spleens and livers than did WT mice. Cytokine assays indicated that baseline interleukin-1␤ and granulocyte colony-stimulating factor (G-CSF) levels were higher in CD18-ko mice than in WT mice and that CD18-ko splenocytes produced higher levels of interleukin-1␤ and G-CSF than WT splenocytes under the same amount of Listeria stimulation. These findings show that CD18 is not an absolute requirement for antilisterial innate immunity or hepatic neutrophil recruitment. We propose that the absence of CD18 in the mice results in the priming of innate immunity, as evidenced by elevated cytokine expression, and neutrophilic leukocytosis, which augments antilisterial defense.

Unique and redundant roles of α4 and β2 integrins in kinetics of recruitment of lymphoid vs myeloid cell subsets to the inflamed peritoneum revealed by studies of genetically deficient mice

“…For example, preferential usage of β2 integin by T-lymphocytes in response to chemoattractive stimuli under shear stress conditions has been reported [48]. In addition, considering pre-existing high systemic levels of inflammatory cytokines in CD18-/-mice [49], the partial defect seen in β2-/-lymphocytes may also be attributed to an attenuated response to TG of already activated CD18-/-lymphocytes by pre-existing inflammatory stimuli.…”

T-Cell Accumulation and Regulated on Activation, Normal T Cell Expressed and Secreted Upregulation in Adipose Tissue in Obesity

“…RNase protection assay was performed with an RNase protection assay starter kit with mouse or human chemokine or chemokine receptor template sets (BD Pharmingen). 15 mRNA quantity of RANTES, CCR5, and MCP-1, where appropriate, was determined by the intensity of the appropriately sized, protected probe fragment relative to that of housekeeping genes GAPDH and/or L32 visualized with a Storm 860 PhosphorImager (Molecular Dynamics). Adiponectin mRNA was examined by Northern blot with GAPDH as an internal control.…”

CD11a Regulates Effector CD8 T Cell Differentiation and Central Memory Development in Response to Infection with Listeria monocytogenes

“…Ϫ/Ϫ mice exhibit enhanced resistance to L. monocytogenes infection, potentially due to neutrophilia, particularly in the liver, as well as enhanced interleukin-12 (IL-12) and granulocyte colony-stimulating factor production (26)(27)(28). In fact, while neutrophils are important for L. monocytogenes clearance from the liver, they play much less of a role in splenic L. monocytogenes clearance, and inflammatory monocytes are essential for protection against L. monocytogenes infection (29)(30)(31).…”