Mucosal immunity to infection with implications for vaccine development

Staats, Herman F.; Jackson, Raymond J.; Marinaro, Mariarosaria; Takahashi, Ichiro; Kanazawa, Hiroshi; McGhee, Jerry R.

doi:10.1016/0952-7915(94)90144-9

Cited by 168 publications

(89 citation statements)

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“…CD4 ϩ T cells are known to be essential for IgA B-cell responses (45). The helper T cells that preferentially produce IL-4, IL-5, IL-6, and IL-10, the Th2 subset of CD4 ϩ T cells, promote IgA responses (15,27,34). Our prior results indicate that intranasal immunization of normal mice with the combined OMPs and CT vaccine induced Th2-type cells in the IgA mucosal response (26).…”

Section: Discussionmentioning

confidence: 99%

“…However, to our knowledge no prior studies investigated the mucosal immune response in the The nasal tract is equipped with a mucosal inductive site in the NALT for the priming of immunocompetent cells to induce antigen-specific mucosal immune responses, such as Peyer's patch in the intestinal tract (2,14,16,24,43). Thus, IgA precursor B cells in NALT are primed and activated by intranasal immunization and then disseminate throughout the mucosal effector sites, including the nasal mucosa and the MEM, via the common mucosal immune system (21,27,34,43,46). Our preliminary study showed that inoculation of the dye into the nose of mice did not result in staining of the middle ear, suggesting that the antigens did not contact the middle ear via intranasal immunization (S. Kodama, M. Suzuki, and G. Mogi, unpublished data).…”

Section: Discussionmentioning

confidence: 99%

“…The mucosal immune system is considered as a separate functional entity quite independent of the systemic immune system because the mucosal immune system possesses unique anatomic features and is composed of specialized subsets of lymphoid cells (21,27,34). Despite the recent emphasis on a better understanding of molecular and cellular aspects of the mucosal immune system, little information is currently available regarding the middle ear mucosa (MEM).…”

mentioning

confidence: 99%

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Induction of Specific Immunoglobulin A and Th2 Immune Responses to P6 Outer Membrane Protein of NontypeableHaemophilus influenzaein Middle Ear Mucosa by Intranasal Immunization

et al. 2000

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Nontypeable Haemophilus influenzae (NTHI) is a major pathogen of otitis media. One of the outer membrane proteins of NTHI, P6, is an antigen common to all strains and is considered as a candidate for mucosal vaccine. To elucidate the possibility of developing a nasal vaccine against nontypeable Haemophilus influenzae (NTHI) and to investigate mucosal immune responses in the middle ear, mice were immunized intranasally with the P6 outer membrane protein of NTHI, and P6-specific immune responses in the middle ear mucosa were examined. Mice were given with P6 and cholera toxin intranasally as an adjuvant on days 0, 7, and 14 and were killed on day 21. The P6-specific immunoglobulin A (IgA) antibody titer in ear wash was significantly elevated. Mononuclear cells were isolated from middle ear mucosa, and an increase in P6-specific IgA-producing cells was shown with an enzyme-linked immunospot assay. In addition, an increase in memory T cells in middle ear mucosa was detected with flow cytometric analysis after intranasal immunization. Moreover, in vitro stimulation with P6 resulted in proliferation of purified CD4 ؉ T cells from immunized mice, and these T cells expressed Th2 cytokine mRNA. These results indicate that P6-specific IgA-B-cell immune responses and selected Th2 cytokine expressing Th cells were induced in middle ear mucosa by intranasal immunization. These findings suggest that a nasal vaccine is useful for preventing otitis media with effusion.Nontypeable Haemophilus influenzae (NTHI) is a major pathogen of otitis media with effusion (OME) and other upper respiratory tract diseases (10, 30). In patients with OME, this bacterium is frequently isolated from the nasopharynx, as well as from middle ear effusions, and the inhibition of NTHI colonization in the upper respiratory tract is considered effective in preventing OME. Due to the increase of antibiotic-resistant strains of NTHI in recent years, the development of a vaccine against this bacterium is considered an important goal for public health. Since NTHI lacks capsular antigens, the chief antigenicity is present in the outer membrane proteins (OMPs). One of the OMPs of NTHI, P6, is a common antigen to all strains and is considered as a candidate for mucosal vaccine (7,9,10,11,30,31).In the mucosal surface, secretory immunoglobulin A (IgA) plays a major role in protective immunity. We previously demonstrated that intranasal immunization was an effective regimen for inducing mucosal IgA immune responses in the upper respiratory tract (26) and that the nasal mucosal IgA immune responses induced by intranasal immunization were effective for the clearance of bacteria in the nasopharynx.The mucosal immune system is considered as a separate functional entity quite independent of the systemic immune system because the mucosal immune system possesses unique anatomic features and is composed of specialized subsets of lymphoid cells (21,27,34). Despite the recent emphasis on a better understanding of molecular and cellular aspects of the mucosal immune system,...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Induction of Specific Immunoglobulin A and Th2 Immune Responses to P6 Outer Membrane Protein of NontypeableHaemophilus influenzaein Middle Ear Mucosa by Intranasal Immunization

et al. 2000

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“…Due to functionally distinct compartmentalization of the immune system, the systemic routes of immunization are usually of limited value for the prevention of some mucosa-contracted infectious diseases, while mucosal immunization is capable of inducing both mucosal and systemic immunity (18,26,46). Thus, induction of strong mucosal immunity is important for the development of effective vaccines.…”

mentioning

confidence: 99%

Mucosal and Systemic Immune Responses to a Human Immunodeficiency Virus Type 1 Epitope Induced upon Vaginal Infection with a Recombinant Influenza A Virus

Garulli

Kawaoka

Castrucci

2004

J Virol

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“…I mmune responses at mucosal surfaces including the intestinal epithelium are characterized by production of IgA and its transport across the epithelium, represents a first line of defense against colonization by viral and bacterial pathogens (1,2). In this regard, the intestinal lamina propria contains the largest number of plasma cells in the host, and Ͼ90% are of IgA isotype.…”

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confidence: 99%

Alternate Mucosal Immune System: Organized Peyer’s Patches Are Not Required for IgA Responses in the Gastrointestinal Tract

Yamamoto

Rennert

McGhee

et al. 2000

The Journal of Immunology

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152

119

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The progeny of mice treated with lymphotoxin (LT)-β receptor (LTβR) and Ig (LTβR-Ig) lack Peyer’s patches but not mesenteric lymph nodes (MLN). In this study, we used this approach to determine the importance of Peyer’s patches for induction of mucosal IgA Ab responses in the murine gastrointestinal tract. Immunohistochemical analysis revealed that LTβR-Ig-treated, Peyer’s patch null (PP null) mice possessed significant numbers of IgA-positive (IgA+) plasma cells in the intestinal lamina propria. Further, oral immunization of PP null mice with OVA plus cholera toxin as mucosal adjuvant resulted in Ag-specific mucosal IgA and serum IgG Ab responses. OVA-specific CD4+ T cells of the Th2 type were induced in MLN and spleen of PP null mice. In contrast, when TNF and LT-α double knockout (TNF/LT-α−/−) mice, which lack both Peyer’s patches and MLN, were orally immunized with OVA plus cholera toxin, neither mucosal IgA nor serum IgG anti-OVA Abs were induced. On the other hand, LTβR-Ig- and TNF receptor 55-Ig-treated normal adult mice elicited OVA- and cholera toxin B subunit-specific mucosal IgA responses, indicating that both LT-αβ and TNF/LT-α pathways do not contribute for class switching for IgA Ab responses. These results show that the MLN plays a more important role than had been appreciated until now for the induction of both mucosal and systemic Ab responses after oral immunization. Further, organized Peyer’s patches are not a strict requirement for induction of mucosal IgA Ab responses in the gastrointestinal tract.

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Mucosal immunity to infection with implications for vaccine development

Cited by 168 publications

References 50 publications

Induction of Specific Immunoglobulin A and Th2 Immune Responses to P6 Outer Membrane Protein of NontypeableHaemophilus influenzaein Middle Ear Mucosa by Intranasal Immunization

Induction of Specific Immunoglobulin A and Th2 Immune Responses to P6 Outer Membrane Protein of NontypeableHaemophilus influenzaein Middle Ear Mucosa by Intranasal Immunization

Mucosal and Systemic Immune Responses to a Human Immunodeficiency Virus Type 1 Epitope Induced upon Vaginal Infection with a Recombinant Influenza A Virus

Alternate Mucosal Immune System: Organized Peyer’s Patches Are Not Required for IgA Responses in the Gastrointestinal Tract

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