Resident Leukocyte Populations of Innate Immune System

Innate immunity depends on both resident and recruited leukocytes. The macrophage without doubt plays an import- ant role in the detection of pulmonary infections. Low inocula of pneumococci are cleared by macrophages. Alveolar macrophages also have an important role in the initiation of responses to inhaled lipopolysaccharide (LPS) and their function is altered by exposure to irritants such as cigarette smoke. Alveolar macrophages may also have a role to play in the regulation of airway hyper-responsiveness. These cells can exhibit strain-dependent bias toward the support of Th1 or Th2 phenotypes and be rendered tolerogenic, resulting in down regulation of allergic airways disease.

There is also evidence that macrophages have additional roles in the maintenance of normal peripheral tolerance in vivo, and alveolar macrophages can inhibit DC maturation in the lung (Holt et al. 1993). These are long-lived cells derived from monocytes, but in chronic inflammation repeated rounds of cell recruitment may result in replacement of macro- phages by cells with a more monocytic phenotype.

Data from the gut and lung has suggested that DCs may sample the local microenvironment by extruding processes through epithelial cell tight junctions: such mechanisms might also be theoretically important in the lung. Clearly the lung is a major site of antigen exposure, and resident DCs have vital roles to play in the regulation of the subsequent inflammatory and immunologic response, acting as a bridge between innate and adaptive immunity (discussed in more detail below). Again, subsets of DCs in the lungs show selective patterns of expression of innate immune receptors such as the TLRs, and differential ability to support T-cell proliferation.

Other cells which act as long-term resident early-warning cells include the lung mast cell. Mast cells respond to pathogenic stimuli in species- and tissue-specific patterns, and through dual signaling via pathogen-response systems and IgE-mediated mechanisms have the potential to integrate innate and adaptive responses into a regulation of Th2 immunity.

Resident T-cell populations that form part of the innate immune system, such as natural killer (NK) and NKT cells, may also exert important roles in allergic inflammation. These cells again respond to agonists stimulating pathogen response systems such as TLRs, though some of these responses may be mediated by indirect networks.