Exposure to Actinobacteria resident in water-damaged buildings and resultant immune injury in Chronic Inflammatory Response Syndrome

Abstract

The indoor air quality literature has expanded to include a wider variety of contaminants responsible for adverse human health effects. The increased use of Next Generation Sequencing (NGS), combined with the advent of transcriptomic assays, has defined specific causation of innate immune activation within this growing list of pathogenic microbes. Here we report the correlation of specific Actinobacteria as shown by NGS, with specific differential gene activation, using a transcriptomic assay (GENIE; Progene Dx, LLC, Bedford, Massachusetts). The study provides newly described indices of dominance (DI) and prevalence (PI) for exposure to Actinobacteria that have enabled clinicians to develop targeted treatment protocols to improve health issues as shown by reduction of symptoms, restoration of normal proteomics and transcriptomics, and correcting molecular hypometabolism (MHM), upregulation of MAPKs and TGFBR, as part of a chronic inflammatory response syndrome (CIRS), acquired following exposure to the interior environment of a water-damaged building (WDB). NGS has shown differences in populations of Actinobacteria found in WDB that are paralleled by differences in innate immune responses. Actinobacteria carried on human skin (HH, human habitat), as opposed to dwelling in soils (SH, soil habitat), consistent with prior publications, can now be represented by DI and PI pinpointing of specific areas of WDB requiring remediation. A review of the literature shows the capability of HH organisms to induce inflammatory processes in skin and systemically. In addition, the rapid expansion of research on extracellular vesicles suggests a reasonable basis for a mechanism by which resident HH initiate a cascade of inflammatory and metabolic events leading to adverse health effects following exposure to Gram-positive organisms, particularly lipophilic Corynebacteria, Cutibacteria and Mycobacteria, all of which contain mycolic acids in their cell walls. The role of unique structural differences in specific mycolic acids stratifying those Actinobacteria that are inflammatory may become fertile ground for the treatment of HH-associated illnesses, including CIRS. A review of the biology of receptors for TGF beta-1 adds to the importance of preventing the downstream signaling from upregulated TGFBR in illness associated with elevated PI. The aim of the paper is to identify distinguishing clinical features, including inflammation and immunoreactivity involving MAPK and TGFBR that are seen in illness associated with indoor exposure to Actinobacteria.