Neutrophil activation in infants hospitalized with severe respiratory viral infection

Background: The immune response to viral respiratory tract infections (vRTI) includes recruitment of circulating neutrophils to the lungs. Recruitment requires cellular activation, which can be measured by CD11b surface expression. Little is known about cell surface expression of CD11b in vRTI. We aim to describe CD11b expression on the circulating neutrophils of infants hospitalized with vRTI.

Methods: Hospitalized infants < 2 years of age with a documented vRTI attributed to a single virus and healthy infant controls were included in the study. After obtaining informed consent, whole blood was collected into a syringe coated with EDTA. Neutrophil CD11b expression was determined using flow cytometry, gating on CD16+ granulocytes following exposure to increasing concentrations of CXCL-1 (0-100 nM), a potent inducer of CD11b surface expression. A sample of infants with vRTI was seen in follow-up at 2, 6 and 10 weeks post-discharge. Whole blood was obtained at each visit for neutrophil CD11b expression analysis.

Results: 12 infants with vRTI were included with a mean age of 75 days (range 11 - 420 days), 4 (33%) were males. 7 healthy infants were included with a mean age of 73 days (range 16 – 129 days), 2 (29%) were males. Infants were diagnosed with human metapneumovirus (HMPV, 2 (17%)), respiratory syncytial virus (RSV, 8 (67%)), and coronavirus (CoV, 2 (17%)). Neutrophils from infected infants exhibited a mean fold increase of 1.1 (range 1-1.3) with increasing concentration gradient of CXCL1 stimulant, compared to healthy infant controls which exhibited a mean fold increase of 3.5 (range 1.3 – 5.7). 5 infants (2 RSV, 2 HMPV, 1 CoV) were seen in follow up. Neutrophils in the infant with vRTI showed recovery of CD11b expression after CXCL1 stimulation between 2 and 10 weeks after discharge.

Conclusion: Circulating neutrophils obtained from vRT-infected infants resist CXCL-1 associated increases in CD11b surface expression suggesting that even prior to recruitment to the airways, circulating neutrophils are already highly activated.