New Insights Gained into the Body’s Reaction to Inhaled Fungi

Newswise — Fungal infections are a major health problem for people whose immune systems are compromised because of genetic deficiencies, AIDS, or cancer and associated medical treatments like chemotherapy. In those people a deficient immune response can permit fungi to take hold in the body and produce severe infection. In addition, exposure to environmental fungi can exacerbate asthmatic reactions.

A key to enhancing protective immunity to fungal infections and potentially modulate harmful inflammatory responses associated with asthma involves understanding how the immune system recognizes and responds to fungal exposure. To that end, Dr. Amariliz Rivera of the University of Medicine and Dentistry of New Jersey-New Jersey Medical School and colleagues have pinpointed a receptor in mice that appears to regulate inflammatory responses induced by inhalation of Aspergillus fumigatus, one of the most common fungi in the environment. Their findings have been published in the Journal of Experimental Medicine (J Exp Med 2011 208:369-381).

The investigators found that signaling through Dectin-1, a cell surface receptor specialized for the recognition of fungi, alters the immune cytokine pattern resulting in a qualitatively different inflammatory response. Working with mice with a genetic deficiency in Dectin-1, the authors discovered that signaling through this receptor inhibits the cytokines IL-12 and interferon gamma. As these cytokines inhibit IL-17 induction, signaling through Dectin-1 results in a commensurate increase in IL-17, a cytokine known to mediate protective effects against fungal infection in humans. The current work by Rivera and colleagues lays the theoretical groundwork for efforts to study and manipulate the immune response to fungi by controlling signaling through the receptors that initially recognize fungal pathogens.

This study was supported by grants from the National Cancer Institute (NCI) and the National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health. Authors, in addition to Rivera, were Tobias M. Hohl of Fred Hutchinson Cancer Research Center; Eric G. Pamer, Nichole Collins, Ingrid Leiner and Jesse W. Coward of Memorial Sloan-Kettering Cancer Center (MSKCC); Alena Gallegos of NIAID; Shinobu Saijo and Yoichiro Iwakura of the University of Tokyo.

About UMDNJ:

The University of Medicine and Dentistry of New Jersey (UMDNJ) is the nation's largest free-standing public health sciences university with more than 6,000 students attending the state's three medical schools, its only dental school, a graduate school of biomedical sciences, a school of health related professions, a school of nursing and its only school of public health on five campuses. Annually, there are more than two million patient visits at UMDNJ facilities and faculty practices at campuses in Newark, New Brunswick/Piscataway, Scotch Plains, Camden and Stratford. UMDNJ operates University Hospital, a Level I Trauma Center in Newark, and University Behavioral HealthCare, which provides a continuum of healthcare services with multiple locations throughout the state.