Neutrophils are dispensable in the modulation of T cell immunity against cutaneous HSV-1 infection

Jyh Liang Hor,William R Heath,Scott N Mueller

doi:10.1038/srep41091

Abstract

Neutrophils rapidly infiltrate sites of inflammation during peripheral infection or tissue injury. In addition to their well described roles as pro-inflammatory phagocytes responsible for pathogen clearance, recent studies have demonstrated a broader functional repertoire including mediating crosstalk between innate and adaptive arms of the immune system. Specifically, neutrophils have been proposed to mediate antigen transport to lymph nodes (LN) to modulate T cell priming and to influence T cell migration to infected tissues. Using a mouse model of cutaneous herpes simplex virus type 1 (HSV-1) infection we explored potential contributions of neutrophils toward anti-viral immunity. While a transient, early influx of neutrophils was triggered by dermal scarification, we did not detect migration of neutrophils from the skin to LN. Furthermore, despite recruitment of neutrophils into LN from the blood, priming and expansion of CD4+ and CD8+ T cells was unaffected following neutrophil depletion. Finally, we found that neutrophils were dispensable for the migration of effector T cells into infected skin. Our study suggests that the immunomodulatory roles of neutrophils toward adaptive immunity may be context-dependent, and are likely determined by the type of pathogen and anatomical site of infection.

Highlights

Introduction(d) Time course depicting total number of Ly6Ghi neutrophils in skin from 6 hr to 45 hr post-scarification
Post-scarification, as shown in (a). (d) Time course depicting total number of Ly6Ghi neutrophils in skin from 6 hr to 45 hr post-scarification. (a–d) Data pooled from 2–5 independent experiments, n = 9–18 mice per group (b,c), n = 5–19 mice per group (d). (e) C57BL/6 mice were intradermally injected with HSV-1 (107 pfu, dark red or 106 pfu, red), S. aureus (107 cfu, dark orange or 106 cfu, orange), PBS or left untreated
Using flow cytometry to follow the recruitment of neutrophils into the skin, we observed significant influx of Ly6Ghi Ly6Cint neutrophils as early as 6 hr p.i. (Fig. 1a) In addition, Ly6Chi monocytes showed an increase in their numbers (Fig. 1a, Supplementary Fig. S1a)

Summary

Introduction

(d) Time course depicting total number of Ly6Ghi neutrophils in skin from 6 hr to 45 hr post-scarification. (f) Time lapse snapshots depicting two-areas of scarified skin (2 hr, top row, and 4 hr, bottom row after HSV-1 infection) at the start of the imaging period (t = 0) and 30 minutes after (t = 30). We investigated whether neutrophils: (1) help enhance antigen transport to the draining LN, and (2) contribute to the priming, expansion and migration of CD4+ and CD8+ T cells during cutaneous HSV-1 infection. We show that while neutrophils infiltrate both the skin and draining LN early after dermal scarification, skin-infiltrating neutrophils do not migrate to draining LN These cells are dispensable for the priming and expansion of primary T cell responses against HSV-1, and are not required for the migration of effector cells into infected skin. Our results argue that contributions by neutrophils in shaping adaptive immunity may be dependent upon the specific context of infection, including the type of pathogen and the anatomical site of infection

Methods

Results

Conclusion