Impairment of Mucosal Immunity by Total Parenteral Nutrition: Requirement for IgA in Murine Nasotracheal Anti-Influenza Immunity

Renegar, Kathryn B.; Johnson, Corey; DeWitt, R. Chance; King, Brock K.; Li, Jian; Fukatsu, Kazuhiko; Kudsk, Kenneth A.

doi:10.4049/jimmunol.166.2.819

Cited by 51 publications

(17 citation statements)

References 37 publications

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“…We cannot exclude the possibility that other protective mechanisms that are not the primary means of protection in the upper RT of wild-type mice, such as elevated levels of IgM and IgG, may become active in congenitally S-IgA-deficient mice. In this regard, Renegar et al (50,51) have demonstrated that genetically normal immune mice, given chemically defined total parenteral nutrition by the i.v. route, results in loss of nasal anti-influenza immunity with a significant drop in influenza-specific S-IgA titer in the upper RT compared with chow-fed mice, suggesting that the impairment of mucosal immunity in genetically normal mice cannot be substituted by serum IgG for the role of S-IgA in the protective immunity against influenza virus infection.…”

Section: Discussionmentioning

confidence: 99%

Protection Against Influenza Virus Infection in Polymeric Ig Receptor Knockout Mice Immunized Intranasally with Adjuvant-Combined Vaccines

Asahi

Yoshikawa

Watanabe

et al. 2002

The Journal of Immunology

193

133

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The role of secretory IgA in conferring cross-protective immunity was examined in polymeric (p)IgR knockout (KO) mice immunized intranasally with different inactivated vaccines prepared from A/PR/8/34 (H1N1), A/Yamagata/120/86 (H1N1), A/Beijing/262/95 (H1N1), and B/Ibaraki/2/85 viruses and infected with the A/PR/8/34 virus in the upper respiratory tract (RT)-restricting volume. In wild-type mice, immunization with A/PR/8/34 or its variant (A/Yamagata/120/86 and A/Beijing/262/95) vaccines conferred complete protection or partial cross-protection against infection, while the B-type virus vaccine failed to provide protection. The protection or cross-protection was accompanied by an increase in the nasal A/PR/8/34 hemagglutinin-reactive IgA concentration, which was estimated to be >30 times the serum IgA concentration and much higher than the nasal IgG concentration. In contrast, the blockade of transepithelial transport of dimeric IgA in pIgR-KO mice reduced the degree of protection or cross-protection, in parallel with the marked increase in serum IgA concentration and the decrease in nasal IgA concentration (∼20 and 0.3 times those in wild-type mice, respectively). The degree of the reduction of protection or cross-protection was moderately reversed by the low but non-negligible level of nasal IgA, transudates from the accumulated serum IgA. These results, together with the absence of the IgA-dependent cross-protection in the lower RT and the unaltered level of nasal or serum IgG in wild-type and pIgR-KO mice, confirm that the actively secreted IgA plays an important role in cross-protection against variant virus infection in the upper RT, which cannot be substituted by serum IgG.

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Section: Discussionmentioning

confidence: 99%

Protection Against Influenza Virus Infection in Polymeric Ig Receptor Knockout Mice Immunized Intranasally with Adjuvant-Combined Vaccines

Asahi

Yoshikawa

Watanabe

et al. 2002

The Journal of Immunology

193

133

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“…with PspA was found to reduce bacterial colonization in the nasal tract compared to that in animals receiving PspA alone, which may be the result of higher levels of IgA in these animals. Indeed, we (2) and others (30,31) have recently provided evidence that IgA is an essential component of mucosal antiviral immunity. Therefore, pneumococal vaccination strategies that augment secretory IgA may be important for protective immunity against nasopharyngeal bacterial carriage as well.…”

Section: Discussionmentioning

confidence: 99%

Intranasal Vaccination with Pneumococcal Surface Protein A and Interleukin-12 Augments Antibody-Mediated Opsonization and Protective Immunity againstStreptococcus pneumoniaeInfection

et al. 2001

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Streptococcus pneumoniae is a major pathogen in humans that enters the host primarily through the respiratory tract. Targeting mucosal surfaces directly may therefore be an optimal approach for vaccination to prevent bacterial colonization and invasive disease. We have previously demonstrated the effectiveness of interleukin-12 (IL-12) delivered intransally (i.n.) as an antiviral respiratory adjuvant. In this study, we examined the effects of i.n. IL-12 treatment on induction of protective humoral immunity against S. pneumoniae. Immunization i.n. with pneumococcal surface protein A (PspA) and IL-12 resulted in enhanced lung IL-10 mRNA expression and marked augmentation of respiratory and systemic immunoglobulin G1 (IgG1), IgG2a, and IgA antibody levels compared to those in animals receiving PspA alone. In addition, i.n. vaccination with PspA and IL-12 provided increased protection against nasopharyngeal carriage. Flow cytometric analysis revealed a threefold increase in antibody-mediated, complement-independent opsonic activity in the sera of PspA-and IL-12-treated animals, which was mainly contributed by IgG2a and, to a lesser extent, IgA. Passive transfer of these immune sera conferred complete protection from death upon systemic pneumococcal challenge. These findings demonstrate the effectiveness of combining PspA and IL-12 at mucosal sites to achieve optimal antibody-mediated opsonization and killing of S. pneumoniae.

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“…We chose the 6 wk point for assessment of serum antiinfluenza virus IgG titers because the murine serum Ab titer is still rising between 3 and 4 wk post-i.n. viral administration (25), but has reached its peak by 6 -8 wk after viral infection (31).…”

Section: Convalescent Serummentioning

confidence: 99%

“…Plasma Ab is sufficient to prevent infection of the lung (15,19), but does not appear to protect the upper respiratory tract of mice and ferrets against viral infection (16,23,24). Plasma influenza virusspecific IgG Ab is also unable to reduce viral shedding in the nasal secretions of normal immune mice with depressed mucosal IgA levels (25). Renegar and Small (10) showed that i.v.…”

mentioning

confidence: 99%

Role of IgA versus IgG in the Control of Influenza Viral Infection in the Murine Respiratory Tract

Renegar

Small

Boykins

et al. 2004

The Journal of Immunology

Self Cite

368

313

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The roles of IgG and secretory IgA in the protection of the respiratory tract (RT) against influenza infection remain unclear. Passive immunization with Ab doses resulting in serum IgG anti-influenza virus Ab titers far in excess of those observed in immune mice has compounded the problem. We compared the effects of i.v. anti-influenza virus IgG and i.v. anti-influenza virus polymeric IgA (pIgA) mAb administered in amounts designed to replicate murine convalescent serum or nasal Ab titers, respectively. A serum anti-influenza virus IgG titer 2.5 times the normal convalescent serum anti-influenza virus IgG titer was required for detectible Ab transudation into nasal secretions, and a serum IgG titer 7 times normal was needed to lower nasal viral shedding by 98%. Anti-influenza virus pIgA at a nasal Ab titer comparable to that seen in convalescent mice eliminated nasal viral shedding. The RT of influenza-infected pIgA- or IgG-protected mice were studied by scanning electron microscopy. Only pIgA was found to prevent virally induced pathology in the upper RT, suggesting that IgG did not prevent viral infection of the nose, but neutralized newly replicated virus after infection had been initiated. In contrast, IgG, but not pIgA, was found to prevent viral pathology in the murine lung. Our results help to resolve the controversy of IgA- vs IgG-mediated protection of the RT; both Abs are important, with plasma IgG Ab serving as the back-up for secretory IgA-mediated protection in the nasal compartment, and IgG being the dominant Ab in protection of the lung.

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Impairment of Mucosal Immunity by Total Parenteral Nutrition: Requirement for IgA in Murine Nasotracheal Anti-Influenza Immunity

Cited by 51 publications

References 37 publications

Protection Against Influenza Virus Infection in Polymeric Ig Receptor Knockout Mice Immunized Intranasally with Adjuvant-Combined Vaccines

Protection Against Influenza Virus Infection in Polymeric Ig Receptor Knockout Mice Immunized Intranasally with Adjuvant-Combined Vaccines

Intranasal Vaccination with Pneumococcal Surface Protein A and Interleukin-12 Augments Antibody-Mediated Opsonization and Protective Immunity againstStreptococcus pneumoniaeInfection

Role of IgA versus IgG in the Control of Influenza Viral Infection in the Murine Respiratory Tract

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