Innate system impairment may result from aberrant receptors signalling,(1,2), lack of innate system proteins (e.g. complement deficiencies),(3,4) or impairment of innate system cells.(5-7)

Toll-like receptors (TLRs) enable recognition of conserved structural motifs characterizing pathogens such as bacteria and viruses. Different clinical manifestations such as severe invasive bacterial infections (e.g., meningitis, sepsis, abscess in internal body organs, and arthritis) (8)or herpes virus encephalitis(9) are associated with specific TLR signaling cascade defects(10).

The complement system is composed of more than 30 serum and membrane-bound proteins that play a major role in innate and adaptive immune defenses(4).Deficiencies of proteins operating in the early classical complement activation cascade are associated with pneumococcal infections and autoimmune diseases ( mainly lupus erythematosus) Recurrent meningitis presenting in young adulthood is most typical of the late component deficiencies and properdin deficiency (11). Vaccination represents the treatment of choice to protect these subjects from recurrent infections(12).

1. Turvey SE, Speert DP. Recurrent systemic pneumococcal disease and IRAK4 deficiency. Pediatr Infect Dis J 2007;26:1074.

2. Turvey SE, Broide DH. Innate immunity. J Allergy Clin Immunol 2010;125:S24-S32.

3. Garcia-Laorden MI, Sole-Violan J, Rodriguez dC, Aspa J, Briones ML, Garcia-Saavedra A et al. Mannose-binding lectin and mannose-binding lectin-associated serine protease 2 in susceptibility, severity, and outcome of pneumonia in adults. J Allergy Clin Immunol 2008;122:368-74, 374.

4. Pettigrew HD, Teuber SS, Gershwin ME. Clinical significance of complement deficiencies. Ann N Y Acad Sci 2009;1173:108-123.

5. Etzioni A. Novel aspects of phagocytic cell disorders. Curr Opin Allergy Clin Immunol 2001;1:535-540.

6. Marsh RA, Satake N, Biroschak J, Jacobs T, Johnson J, Jordan MB et al. STX11 mutations and clinical phenotypes of familial hemophagocytic lymphohistiocytosis in North America. Pediatr Blood Cancer 2010;55:134-140.

7. Gupta R, Sheikh A, Strachan DP, Anderson HR. Time trends in allergic disorders in the UK. Thorax 2007;62:91-96.

8. Day N, Tangsinmankong N, Ochs H, Rucker R, Picard C, Casanova JL et al. Interleukin receptor-associated kinase (IRAK-4) deficiency associated with bacterial infections and failure to sustain antibody responses. J Pediatr 2004;144:524-526.

9. Sancho-Shimizu V, Zhang SY, Abel L, Tardieu M, Rozenberg F, Jouanguy E et al. Genetic susceptibility to herpes simplex virus 1 encephalitis in mice and humans. Curr Opin Allergy Clin Immunol 2007;7:495-505.

10. Suhir H, Etzioni A. The role of Toll-like receptor signaling in human immunodeficiencies. Clin Rev Allergy Immunol 2010;38:11-19.

11. Ross SC, Densen P. Complement deficiency states and infection: epidemiology, pathogenesis and consequences of neisserial and other infections in an immune deficiency. Medicine (Baltimore) 1984;63:243-273.

12. Tedesco F. Inherited complement deficiencies and bacterial infections. Vaccine 2008;26 Suppl 8:I3-I8.