Contact lens wear is a common form of vision correction with more than 140 million wearers worldwide. Contact lens-associated complications affecting the cornea and conjunctiva include inflammatory events, ocular discomfort, dry eye disease and infection (microbial keratitis) [[1], [2], [3], [4], [5], [6], [7]]. While significant progress has been made in understanding the mechanisms of contact lens-associated adverse events, there is still much to learn about their underlying etiology.

In recent years, it has become evident that contact lens wear can be associated with subclinical changes in corneal immune cells, e.g. increased numbers of Langerhans cells, as early as 2 h of wear [8], that are also evident after 7 days [4]. It was proposed that human contact lens wear is “intrinsically inflammatory” and that lens-induced parainflammation may serve to protect the cornea against noxious external stimuli [9]. More recently, we reported development of a contact lens wearing murine model of microbial keratitis, in which lens-induced parainflammatory events in the cornea were observed that resembled changes in Langerhans cells observed during lens wear in humans [10]. These contact lens-induced changes were: a significant increase in corneal CD11c+ (dendritic) cells after 24 h and recruitment of Ly6G + cells (neutrophils) to the cornea after 5–6 days. Since both of these cellular responses occurred without obvious clinical signs, they were termed parainflammatory [10].

Parainflammation was described previously as a response to tissue stress that resided between the basal homeostatic state of a tissue and classical “symptomatic” inflammation [11]. Our long-term goal is to understand the mechanisms and clinical significance of contact lens-induced corneal parainflammation. Do these clinically silent changes in corneal CD11c + cells and Ly6G + cells during lens wear represent protective adaptations or the first step in predisposing the cornea to clinically evident adverse events?

In the present study, we focused on the mechanisms by which Ly6G + cells are recruited to the cornea after 6 days of lens wear. Recruitment of Ly6G + cells (neutrophils) to a site of injury or infection is typically associated with many different types of signaling via complement proteins (C5a), leukotrienes (LTB4) cytokines (IL-6, IL-8, IL-17) and chemokines (CXCL1, CXCL2) [[12], [13], [14], [15]]. The murine model of contact lens wear was used to test the hypothesis that IL-17 mediated signaling was involved. This hypothesis was based on two prior observations: 1) IL-17 produced by ocular surface γδ T cells in response to conjunctival colonization by a commensal Corynebacterium sp. was important for neutrophil homeostasis in the conjunctiva and recruitment of these cells to defend the cornea against Pseudomonas aeruginosa and Candida albicans infection [16], and 2) our recent observation that CD11c + cell corneal parainflammatory responses to 24 h of contact lens wear were prevented by antibiotic treatment correlating with changes in viability/activity of conjunctival commensal bacteria [17].

Using IL-17A- and F-deficient mice and antibody depletion of γδ T cells, we found evidence that an early recruitment of IL-17 producing γδ T cells to the cornea of contact lens-wearing mice precipitates IL-17A (but not F)-dependent recruitment of neutrophils to the cornea, serving as a trigger of contact lens-induced parainflammation.