title: Lack of the pattern recognition molecule mannose-binding lectin increases susceptibility to influenza A virus infection.
abstract: BACKGROUND
  Mannose-binding lectin (MBL), a pattern recognition innate immune molecule, inhibits influenza A virus infection in vitro. MBL deficiency due to gene polymorphism in humans has been associated with infection susceptibility. These clinical observations were confirmed by animal model studies, in which mice genetically lacking MBL were susceptible to certain pathogens, including herpes simplex virus 2.
  
  
  RESULTS
  We demonstrate that MBL is present in the lung of naïve healthy wild type (WT) mice and that MBL null mice are more susceptible to IAV infection. Administration of recombinant human MBL (rhMBL) reverses the infection phenotype, confirming that the infection susceptibility is MBL-mediated. The anti-viral mechanisms of MBL include activation of the lectin complement pathway and coagulation, requiring serum factors. White blood cells (WBCs) in the lung increase in WT mice compared with MBL null mice on day 1 post-infection. In contrast, apoptotic macrophages (MΦs) are two-fold higher in the lung of MBL null mice compared with WT mice. Furthermore, MBL deficient macrophages appear to be susceptible to apoptosis in vitro. Lastly, soluble factors, which are associated with lung injury, are increased in the lungs of MBL null mice during IAV infection. These results suggest that MBL plays a key role against IAV infection.
  
  
  CONCLUSIONS
  MBL plays a key role in clearing IAV and maintaining lung homeostasis. In addition, our findings also suggest that MBL deficiency maybe a risk factor in IAV infection and MBL may be a useful adjunctive therapy for IAV infection.
authors.affiliation: Department of Pediatrics, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors.forename: Wei-Chuan
authors.initials: WC
authors.lastname: Chang
authors.forename: Mitchell R
authors.initials: MR
authors.lastname: White
authors.forename: Patience
authors.initials: P
authors.lastname: Moyo
authors.forename: Sheree
authors.initials: S
authors.lastname: McClear
authors.forename: Steffen
authors.initials: S
authors.lastname: Thiel
authors.forename: Kevan L
authors.initials: KL
authors.lastname: Hartshorn
authors.forename: Kazue
authors.initials: K
authors.lastname: Takahashi
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000821:virology; D003167:Complement Activation / Q000276:immunology; D004198:Disease Susceptibility / Q000276:immunology* / Q000821:virology*; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000821:virology*; D007958:Leukocyte Count; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000821:virology; D037601:Mannose-Binding Lectin / Q000172:deficiency* / Q000378:metabolism; D051379:Mice; D009500:Neutralization Tests; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000821:virology*; D011485:Protein Binding; D051192:Receptors, Pattern Recognition / Q000172:deficiency* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012995:Solubility; D013917:Thrombin / Q000378:metabolism; D019562:Viral Load
chemical_list: D037601:Mannose-Binding Lectin; D051192:Receptors, Pattern Recognition; D011994:Recombinant Proteins; D013917:Thrombin