Correspondence

Dectin-1 Deficiency and Mucocutaneous Fungal Infections

N Engl J Med 2010; 362:367-368January 28, 2010

Article

To the Editor:

Mucocutaneous candidiasis is commonly seen in persons with deficient T-cell–mediated immunity, including newborn infants, patients with the acquired immunodeficiency syndrome, and those with genetically defined primary T-cell deficiencies.1 In their Brief Report about human dectin-1 deficiency and mucocutaneous fungal infections, Ferwerda et al. (Oct. 29 issue)2 suggest that chronic mucocutaneous candidiasis may also be caused by a genetic defect of the β-glucan receptor dectin-1. However, their data should be interpreted with caution. First, they provide no information about how dectin-1 deficiency impairs overall T-cell–dependent mucosal immunity against candida. Second, they suggest that the lack of invasive fungal infection in dectin-1–deficient patients may be attributed to the normal phagocytosis and killing of candida by granulocytes. This explanation sounds reasonable but conflicts with observations of invasive microbial disease in patients with other, recently described innate immune deficiencies.3,4 Finally, it is difficult to define the precise immunologic role of dectin-1 in immunity to candida in light of the demonstration by Saijo et al.5 that dectin-1 may not actually be required for host defense against Candida albicans.

László Maródi, M.D.
Melinda Erdös, M.D.
University of Debrecen, Debrecen, Hungary
lmarodi@dote.hu

No potential conflict of interest relevant to this letter was reported.

5 References

1. 1

   Marodi L. Local and systemic host defense mechanisms against Candida: immunopathology of candidal infections. Pediatr Infect Dis J 1997;16:795-801
   CrossRef | Web of Science | Medline

2. 2

   Ferwerda B, Ferwerda G, Plantinga TS, et al. Human dectin-1 deficiency and mucocutaneous fungal infections. N Engl J Med 2009;361:1760-1767
   Full Text | Web of Science | Medline

3. 3

   Ku CL, Picard C, Erdos M, et al. IRAK-4 and NEMO mutations in otherwise healthy children with recurrent invasive pneumococcal disease. J Med Genet 2007;44:16-23
   CrossRef | Web of Science | Medline

4. 4

   von Bernuth H, Picard C, Jin Z, et al. Pyogenic bacterial infections in humans with MyD88 deficiency. Science 2008;321:691-696
   CrossRef | Web of Science | Medline

5. 5

   Saijo S, Fujikado N, Furuta T, et al. Dectin-1 is required for host defense against Pneumocystis carinii but not against Candida albicans. Nat Immunol 2007;8:39-46
   CrossRef | Web of Science | Medline

Author/Editor Response

In response to Maródi and Erdös: T-cell–derived immunity, and especially responses of type 17 helper T cells (Th17), are crucial for mucosal antifungal defense.1,2 Our report describes deficient Th17-cell responses in patients with dectin-1 deficiency,3 and a similar defect has been reported in persons with defective CARD9, the caspase recruitment domain–containing protein 9.3 The fact that dectin-1 deficiency increases susceptibility to mucocutaneous, but not systemic, fungal infections stresses the specific role that dectin-1 may have in mucosal antifungal host defense. This is not in conflict with a role of NEMO (the inhibitor of kappa light polypeptide gene enhancer in B cells, kinase gamma), IRAK-4 (the interleukin-1 receptor–associated kinase 4), or MyD88 (the protein encoded by myeloid differentiation primary response gene 88) for the host defense against systemic bacterial or fungal infections, since these are adaptor molecules specific for toll-like receptors, a different class of pattern-recognition receptors.4 The suggestion by Saijo et al.5 in their study that dectin-1 is not involved in the host defense against systemic candidiasis in mice reinforces the conclusion that dectin-1 may be specific for mucosal antifungal defense.

Gerben Ferwerda, Ph.D., M.D.
Bart Jan Kullberg, Ph.D., M.D.
Mihai G. Netea, Ph.D., M.D.
Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands
m.netea@aig.umcn.nl

Since publication of their article, the authors report no further potential conflict of interest.

5 References

1. 1

   Conti HR, Shen F, Nayyar N, et al. Th17 cells and IL-17 receptor signaling are essential for mucosal host defense against oral candidiasis. J Exp Med 2009;206:299-311
   CrossRef | Web of Science | Medline

2. 2

   Milner JD, Brenchley JM, Laurence A, et al. Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome. Nature 2008;452:773-776
   CrossRef | Web of Science | Medline

3. 3

   Glocker E-O, Hennigs A, Nabavi M, et al. A homozygous CARD9 mutation in a family with susceptibility to fungal infections. N Engl J Med 2009;361:1727-1735
   Full Text | Web of Science | Medline

4. 4

   Netea MG, Van Der Graaf CA, Vonk AG, Verschueren I, Van Der Mer JW, Kullberg BJ. The role of toll-like receptors (TLR) 2 and TLR4 in the host defense against disseminated candidiasis. J Infect Dis 2002;185:1483-1489
   CrossRef | Web of Science | Medline

5. 5

   Saijo S, Fujikado N, Furuta T, et al. Dectin-1 is required for host defense against Pneumocystis carinii but not against Candida albicans. Nat Immunol 2007;8:39-46
   CrossRef | Web of Science | Medline

Citing Articles (1)

Citing Articles

1. 1

   Joshua D Milner. (2011) IL-17 producing cells in host defense and atopy. Current Opinion in Immunology 23:6, 784-788
   CrossRef