Adverse immunological imprinting by cytomegalovirus sensitizing for allergic airway disease

Abstract

Cytomegalovirus (CMV) infection has a profound impact on the host's immune system. Immunological imprinting by CMV is not restricted to immunity against CMV itself, but can affect immunity against other viral or non-viral infectious agents and also immunopathological responses. One category is heterologous immunity based on molecular mimicry, where antigen recognition receptors specific for a CMV antigen with broad avidity distribution also bind with some avidity to unrelated antigens and exert effector functions against target structures other than those linked to CMV. Another category is induction of cytokines by CMV infection that inhibit or drive immune responses to bystander antigens unrelated to CMV, and a third category is the activation of antigen-presenting cells by CMV from which unrelated antigens profit as "stowaways". A striking example of the "stowaway" category, actually one that is of medical importance, has been published recently and will be discussed here for the more general reader. Specifically, in a murine model, CMV airway infection and inhaled environmental antigen of poor intrinsic allergenic potential were found to sensitize for allergic airway disease (AAD) only when combined. As to the mechanism, viral activation of CD11b + conventional dendritic cells (CD11b + cDC) that localize to airway mucosa facilitates uptake and processing of inhaled antigen. Thus, CMV serves as a "door opener" for otherwise harmless environmental antigens that have no intrinsic property to activate DC. Antigen-laden CD11b + cDC migrate selectively to the airway draining lymph nodes, where they prime type-2 CD4 + T helper (Th-2) cells. Upon airway re-exposure to the inhaled antigen, Th-2 cells secrete interleukins (IL-4, IL-5, IL-9, and IL-25) known to induce goblet cell metaplasia, the lead histopathological manifestation of AAD that is characterized by thickening of airway epithelia and increased numbers of mucus-producing goblet cells, resulting in enhanced mucus secretion and airflow obstruction.

Lower CMV and EBV Exposure in Children With Kawasaki Disease Suggests an Under-Challenged Immune System

“…CMV is known to challenge the immune system, altering the immune response to other pathogens (85). Both EBV and CMV cause a redistribution in B-cell subsets (86)(87)(88).…”

Mast Cells Meet Cytomegalovirus: A New Example of Protective Mast Cell Involvement in an Infectious Disease

“…Thereby, the virus reaches the mucosal surfaces of the upper and lower airways [64][65][66]. As we have shown in the mouse model, mCMV airway infection can promote allergic airway disease by activating migratory dendritic cells [67,68], and airway challenge infection of latently infected mice can recruit effector-memory CD8 T cells from the vascular compartment to the alveolar epithelium [69]. It is, thus, more than likely that CMVs meet MC at respiratory tract surfaces and that MC do not remain uninvolved.…”

The potential roles of interleukin-25 in infectious diseases

“…Haiyu et al found that influenza virus (IAV) more powerfully induced the expression of IL-25 in vitro, and IL-25 positively correlated with the load of IAV (103). A respiratory allergic reaction caused by cytomegalovirus (CMV) is also associated with IL-25 secretion (104). IL-25 treatment exacerbates mouse intestinal West Nile virus (WNV) infection (105).…”