Finally, diabetes mellitus, corticoid steroids therapy, COPD, and antibiotics are risk factors for developing IA. Corticosteroids are immunosuppressive.
Treated alveolar macrophages (AM) can internalize mold conidia (Philippe et al, 2003). However, the corticosteroids inhibit reactive oxidant intermediates, e.g. NADPH oxidase, as well as the production of cytokines TNF-alpha and IL-1 (Taramelli et al, 1996; Philippe et al, 2003; Kamberi et al, 2002).
Although the conidia are internalized, the killing of conidia by the inhibited AM is significantly reduced, allowing the development of IA (Brummer et al, 2001; Philippe et al, 2003; Gangneux et al, 2008).
Corticosteroid use is a major risk factor for the increase in IA in nonneutropenic cases (Trof et al, 2007; Gangneux, et al, 2008). The use of corticosteroids to treat IA becomes more perilous when the toxic metabolite, Gliotoxin, which is produced by several genera of molds, is considered.
Gliotoxin is an immunosuppressive mycotoxin produced by Aspergillus fumigatus, niger, terreus and niger, several Penicillium species, Trichoderma virens and Candida albicans. It has been detected in the sera and lungs of both mice and humans with Aspergillosis (Gardiner et al, 2005; Lewis et al, 2005a, b). Thus, therapy induced immunosuppression probably leads to fungal metabolite immune suppression.
Th-1 cell-mediated immunity was believed to be the major defense against fungal infections, while Th-2 humoral immunity plays a minor role (Blanco and Garcia, 2008). However, recent information suggests that Th-17 cells and IL23/IL17 are important in Aspergillus infections and fungal pathology (Romagnani, 2008; Romani et al, 2008; Tesmer et al, 2008; Zelante et al, 2007, 2008). In this scenario IL-23/IL-17/TGF-beta worsen the infection, while IL-6 has a protective role.
The regulatory pathway in the pathogenic inflammation to molds involves the kynurenines (Belladonna et al, 2006; Romani and Puccetti, 2008). In addition, the acute phase long Pentraxin 3 (PTX3) appears to have a role in the inflammatory process caused by molds (Gaziano et al, 2004).
In mice, the Th-17 cell develops from naive CD4 T cells, while in humans its origin maybe from Tregs or Th-1 cells (Romagnani, 2008). Th-17 was initially described in autoimmune mouse models of autoimmunity: encephalomyelitis (EAE) and collagen-induced arthritis (CIA).
Human Th-17 cells promote disruption of blood brain barrier tight junctions, promote CNS inflammation and kill human neurons through recruitment of CD4+ lymphocytes (Kebir et al, 2007).
Furthermore, the interleukin, IL-17, secreted by Th-17 lymphocytes is elevated in the sera and diseased tissues from various chronic inflammatory diseases: e.g., Crohn’s disease, lupus erythematosus, and rheumatoid arthritis. However, in autistic children plasma IL-17 is not elevated, while IL-23 is decreased (Enstrom et al, 2008). It is also likely that Th-17 cells and IL-17 are involved in severe asthma complicated by bacterial infections independent of IgE-mediated allergic disorders (Romagnani, 2008).
The pentraxins are a family of multimeric pattern-recognition proteins. They are divided into short (C-reactive protein) and long (PTX3) pentraxins (Mantovani et al, 2008)).
Long PTX3 expression is induced in response to inflammatory signals at sites of inflammation. It is secreted by endothelial cells, monocytes/macrophages, dendritic cells (DCs), smooth muscle cells, fibroblasts and is stored in neutrophil granules (Imamura et al, 2007; Jaillon et al, 2007; Savchenko et al, 2008).
Long PTX3 is expressed in individuals with chronic systemic inflammation (Muller et al, 2001; Savchenko et al, 2008). PTX3 is an acute-phase protein produced at sites of infections and is thought to have a protective role against microbial infections, e.g., bacteria, fungi, viruses (He et al, 2007). However, over expression of long PTX3 is associated with more severe in lung injury and correlates with the state of severity of critical illness as well as organ failures (Muller et al, 2001; He et al, 2007; Mauri et al, 2008; Suliman et al, 2008).
Thus, in a mouse model of Aspergillosis depending upon the therapeutic dose PTX3 either exacerbated or improved the state of pulmonary inflammation (Gaziano et al, 2004). Finally, long PTX3 is expressed in the CNS of mice following instillation of LPS and during infections by either Candida albicans or Cryptococcus neoformans (Polentarutti et al, 2000).
IMPORTANT NOTE: Dr. Thrasher is often involved in discussions on the subject of indoor airborne mold spores. According to the CDC, NIOSH, EPA and WHO, such counts do not demonstrate actual contamination. Dr. Thrasher recommends that PCR DNA analysis is used to determine mold species in bulk samples and carpet dust to identify molds species. In addition, dust samples from areas not normally dusted gives historical information vs areas that are frequently cleaned. Along with this, testing can be done to determine the presence of mycotoxins in bulk samples. as well as in fine particulates that are present in the indoor air.
Learn more from Dr. Thrasher about proper methods for sampling and Testing
To see a list of health effects of certain molds, review Table 2
from Dr. Thrasher's paper on Biocontaminants.