Abstract
Human Papillomaviruses (HPVs) 6 and 11 are part of a large family of small DNA viruses, some of which are commensal. Although much of the population can contain or clear infection with these viruses, there is a subset of individuals who develop persistent infection that can cause significant morbidity and on occasion mortality. Depending on the site of infection, patients chronically infected with these viruses develop either recurrent, and on occasion, severe genital warts or recurrent respiratory papillomas that can obstruct the upper airway. The HPV-induced diseases described are likely the result of a complex and localized immune suppressive milieu that is characteristic of patients with persistent HPV infection. We review data that documents impaired Langerhans cell responses and maturation, describes the polarized adaptive T-cell immune responses made to these viruses, and the expression of class select II MHC and KIR genes that associate with severe HPV6 and 11 induced disease. Finally, we review evidence that documents the polarization of functional TH2 and T-regulatory T-cells in tissues persistently infected with HPV6 and 11, and we review evidence that there is suppression of natural killer cell function. Together, these altered innate and adaptive immune responses contribute to the cellular and humoral microenvironment that supports HPV 6 and 11-induced disease.
Highlights
Human papillomaviruses (HPVs) comprise a large family of viruses which are considered to be part of the normal flora of the human epithelium
The adaptive immune response is polarized by the failure of Langerhans cells to mature and present peptides to T-cells, which results in altered/impaired Langerhans cell (LC) signaling that results in a TH2 T-cell bias, which when combined with the lack of natural killer (NK) activity, results in persistent Human Papillomaviruses (HPVs)-induced disease
If it can be confirmed that LCs are the source of CCL17 and CCL22 in HPV 6 and 11-induced papillomas, it would suggest that LCs play an active role in creating and maintaining local immune suppression by recruiting T regulatory cells into HPV 6 and 11 infected epithelial tissues
Summary
Human papillomaviruses (HPVs) comprise a large family of viruses which are considered to be part of the normal flora of the human epithelium. Gene expression of patients with RRP who have persistent HPV 6 and 11 infection [8,9,10] These responses are associated with select class II MHC expression that clearly polarizes T-cell responses towards TH2-like regulatory T-cell (Treg) function [11,12,13]. We have reported that patients with RRP have a restricted natural killer cell immunoglobulin-like receptor (KIR) gene haplotypes that associates with increased NK cell numbers with reduced killing capacity [14] These skewed adaptive and innate responses are demonstrated in patients with RRP, and may be similar to HPV 6/11 induced disease at other anatomical sites.
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