Immunoglobulin A-deficient mice exhibit altered T helper 1-type immune responses but retain mucosal immunity to influenza virus.
We have previously demonstrated that immunoglobulin A (IgA)(-/-) knockout (KO) mice exhibit levels of susceptibility to influenza virus infection that are similar to those of their normal IgA(+/+) littermates. To understand the mechanism of this apparent mucosal immunity without IgA, immunoglobulin isotype and T helper 1 (Th1)-type [interferon-gamma (IFN-gamma)] and Th2-type [interleukin (IL)-4, IL-5)] cytokine responses to influenza vaccine were evaluated. Intranasal immunization with influenza virus subunit vaccine plus cholera toxin/cholera toxin B subunit (CT/CTB) induced significant influenza virus-specific immunoglobulin G (IgG) antibody in the serum and nasal passages of both IgA(-/-) and IgA(+/+) mice, while IgA antibodies were induced only in IgA(+/+) mice. IgA KO mice exhibited an IgG1 subclass haemagglutinin (HA)-specific response but no detectable IgG2a and IgG2b responses. In contrast, IgA(+/+) mice exhibited significant IgG1 as well as IgG2a responses. This indicates a predominant Th2-type response in IgA KO mice compared to normal mice. Following stimulation with influenza virus in vitro, splenic lymphocytes from immunized IgA(-/-) mice produced significantly lower levels of IFN-gamma than IgA(+/+) mice (P < 0.001), but elaborated similar levels of IL-4 and IL-5. This was true at both protein and mRNA levels. Immunized mice were challenged intranasally with a small inoculum of influenza virus to allow deposition of virus in the nasal mucosal passages. Compared to non-immunized mice, immunized IgA(-/-) and IgA(+/+) mice exhibited significant, but similar levels of reduction in virus titres in the nose and lung. These results demonstrate that in addition to IgA deficiency, IgA gene deletion also resulted in down-regulated Th1-type immune responses and confirm our previous data that IgA antibody is not indispensable for the prevention of influenza virus infection.
Zhang
Yongxin
Y
Influenza Research Center, Respiratory Pathogens Research Unit, Department of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030, USA.
Pacheco
Susan
S
Acuna
Catherine L
CL
Switzer
Kirsten C
KC
Wang
Ying
Y
Gilmore
Xyanthine
X
Harriman
Gregory R
GR
Mbawuike
Innocent N
IN
D000818:Animals; D017353:Gene Deletion; D017098:IgA Deficiency / Q000276:immunology*; D018928:Immunity, Mucosal; D007070:Immunoglobulin A / Q000235:genetics / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis; D007252:Influenza Vaccines / Q000276:immunology*; D007371:Interferon-gamma / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D051379:Mice; D018345:Mice, Knockout; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D018417:Th1 Cells / Q000276:immunology*; D014611:Vaccination / Q000379:methods
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007252:Influenza Vaccines; D015848:Interleukin-5; D015847:Interleukin-4; D007371:Interferon-gamma