Immunity to a pulmonary Cryptococcus neoformans infection requires both CD4+ and CD8+ T cells.

Huffnagle, Gary B.; Yates, Judy L.; Lipscomb, Mary F.

doi:10.1084/jem.173.4.793

Cited by 244 publications

(181 citation statements)

References 47 publications

Supporting

Mentioning

172

Contrasting

Unclassified

Order By: Relevance

“…Classically, defects in cellular immunity, particularly those that require T lymphocytes, are considered as the main risk factor for the mycosis, both in humans and mice (3,4). In the present study, it was observed that the susceptible mouse strain produced the highest amount of crossreactive antibodies.…”

Section: Discussionsupporting

confidence: 51%

“…C. neoformans has a polysaccharide capsule composed of glucuronoxylomannan (GXM), which acts as a major virulence factor (2) and is considered to be a thymus independent type-2 antigen (TI-2). A murine model in which C. neoformans is inoculated via intratracheal route has allowed the definition of different levels of susceptibility among the various mouse strains (3,4). It has been proposed that these differences are attributed mainly to the presence of a Th1 cellular immune response (3).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Producción de anticuerpos IgG1 anti-glucuronoxilomanana en ratones resistentes a la criptococosis

Parra¹,

González²,

Castañeda

et al. 2005

biomedica

View full text Add to dashboard Cite

Background. Cryptococcus neoformans is a widely disseminated fungus shown to be responsible for infections in individuals with impaired cell mediated immunity, such as patients with human immunodeficiency virus (HIV). Cryptococcus neoformans has a polysaccharide capsule composed of glucuronoxylomannan (GXM), which acts as a major virulence factor and is considered to be a thymus independent type-2 antigen (TI-2).Objective. In the current study, the production kinetics were evaluated for IgG subclasses specific for GXM, and assessed with the cross reactive antibodies to Streptococcus pneumoniae polysaccharide. In addition, spleen B cell subpopulations were quantified in murine models of cryptococcosis with different susceptibilities to the infection. Material and methods. Antibodies were detected by ELISA at different time intervals after C. neoformans infection in moderately resistant (Balb/c), highly resistant (CBA/j) and susceptible (C57BL/6) mouse strains. B cells subpopulations were determined by flow cytometry analysis. Results. Early production of IgG 1 , described as protector antibodies, coincided with a decrease of the number of C. neoformans colony forming units in the lungs. Polysaccharide cross-reactive antibodies were detected in each of the three mouse strains. Antibody titers were highest in the susceptible strain (C57BL/6), a strain which also showed the highest proportion of splenic CD5 + B lymphocytes. In contrast, CBA/J mice showed the highest levels of CD43 + B. Conclusions. These findings suggest that IgG 1 antibodies specific for GXM, are implicated in host protection against C. neoformans infection and may be regulated by CD43 + cells. They also suggest that cross reactivity antibodies are not important in the protection against C. neoformans infection.

show abstract

Section: Discussionsupporting

confidence: 51%

mentioning

confidence: 99%

Producción de anticuerpos IgG1 anti-glucuronoxilomanana en ratones resistentes a la criptococosis

Parra¹,

González²,

Castañeda

et al. 2005

biomedica

View full text Add to dashboard Cite

show abstract

“…33 Th cells are central regulators of anticryptococcal immune responses. 25,34,35 Although Th2 responses are detrimental, 11,15 Th1 and Th17 responses are protective. 7,9,25,35,36 To gain a deeper insight into the Th cytokine profile in the absence of eosinophils, we analyzed IL-4, IFN-␥, and IL-17A production by pulmonary Th cells on infection of WT and eosinophil-deficient ⌬dblGATA mice.…”

Section: In the Absence Of Eosinophils Th2 Responses Are Reduced Andmentioning

confidence: 99%

Eosinophils Contribute to IL-4 Production and Shape the T-Helper Cytokine Profile and Inflammatory Response in Pulmonary Cryptococcosis

Piehler

Stenzel

Grahnert

et al. 2011

The American Journal of Pathology

View full text Add to dashboard Cite

Susceptibility to infection with Cryptococcus neoformans is tightly determined by production of IL-4. In this study, we investigated the time course of IL-4 production and its innate cellular source in mice infected intranasally with C. neoformans. We show that pulmonary IL-4 production starts surprisingly late after 6 weeks of infection. Interestingly, in the lungs of infected mice, pulmonary T helper (Th) cells and eosinophils produce significant amounts of IL-4. In eosinophil-deficient ⌬dblGATA mice, IL-33 receptor-expressing Th2s are significantly reduced, albeit not absent, whereas protective Th1 and Th17 responses are enhanced. In addition, recruitment of pulmonary inflammatory cells during infection with C. neoformans is reduced in the absence of eosinophils. These data expand previous findings emphasizing an exclusively destructive effector function by eosinophilic granulocytes. Moreover, in ⌬dblGATA mice, fungal control is slightly enhanced in the lung; however, dissemination of Cryptococcus is not prevented. Therefore, eosinophils play an immunoregulatory role that contributes to Th2-dependent susceptibility in allergic inflammation during bronchopulmonary mycosis. Cryptococcus neoformans is a facultative intracellular pathogen that is acquired by inhalation of spores and/or desiccated yeasts and leads to latent pulmonary infection in immunocompetent humans. 1 The development of cryptococcal meningitis occurs mainly in immunocompromised HIV-1-infected patients, most likely by reactivation of latent pulmonary C. neoformans infection. 2 It is estimated that 504,000 HIV-1-infected patients die every year from cryptococcal meningitis in sub-Saharan Africa, 3 which surprisingly exceeds the annual death rate of tuberculosis-associated HIV cases. Resistance against C. neoformans primarily involves monocytic effector mechanisms. 4 -6 In this context, T helper (Th) cells are central regulatory players with profound effects. Whereas IL-12-dependent Th1 responses are protective, with an additional contribution by IL-23-dependent Th17 responses, 7-9 Th2 cells producing IL-4, IL-13, and IL-5 are detrimental. 10,11 Studies 12-14 that used i.v. inoculation examined the traversal of the blood-brain barrier by C. neoformans and led to the conclusion that transmigration can occur with intracellular and extracellular fungi. In case of bronchopulmonary infection, dissemination seems to rely more on Th2 cytokines. This allergic Th2-driven inflammation represents the immunopathological pathway promoting disease by allowing cryptococci to grow inside the lung and finally enabling dissemination to the brain, ultimately causing fatal meningoencephalitis. 15 This sequela is accompanied by development of IL-4/IL-13-dependent alternatively activated macrophages, suggesting that those cells may be involved in dissemination. Alternatively activated macrophages are found only in susceptible mice 15 and show significantly reduced control of intracellular growth. 5 In addition, IL-13-dependent mucus production by goblet cells, IL-4 -...

show abstract

“…In immune deficient patients, dissemination of the pathogen occurs due to the inability of the host to limit the infection (21,22). Protection from C. neoformans infection depends on both CD4 ϩ and CD8 ϩ T cells (23)(24)(25)(26). Although both lymphocyte subsets may affect the pathogen directly, indirect immune activation of NK cells (27), neutrophils, and macrophages (28) may also confer host resistance.…”

Section: O Ptimal Activation Of Naive T Cells Requires Two Signalsmentioning

confidence: 99%

OX40 Ligation on Activated T Cells Enhances the Control ofCryptococcus neoformansand Reduces Pulmonary Eosinophilia

Humphreys

Edwards

Walzl

et al. 2003

The Journal of Immunology

View full text Add to dashboard Cite

Pulmonary eosinophilia induced in C57BL/6 mice after Cryptococcus neoformans infection is driven by CD4+ Th2 cells. The immunological mechanisms that protect against eosinophilia are not fully understood. Interaction of OX40 (CD134) and its ligand, OX40L, has been implicated in T cell activation and cell migration. Unlike CD28, OX40 is only expressed on T cells 1–2 days after Ag activation. Manipulation of this pathway would therefore target recently activated T cells, leaving the naive repertoire unaffected. In this study, we show that engagement of OX40 by an OX40L:Ig fusion protein drives IFN-γ production by CD4+ T cells and reduces eosinophilia and C. neoformans burden in the lung. Using gene-depleted mice, we show that reduction of eosinophilia and pathogen burden requires IL-12 and/or IFN-γ. C. neoformans infection itself only partially induces OX40L expression by APCs. Provision of exogenous OX40L reveals a critical role of this pathway in the prevention of C. neoformans-induced eosinophilia.

show abstract

Immunity to a pulmonary Cryptococcus neoformans infection requires both CD4+ and CD8+ T cells.

Cited by 244 publications

References 47 publications

Producción de anticuerpos IgG1 anti-glucuronoxilomanana en ratones resistentes a la criptococosis

Producción de anticuerpos IgG1 anti-glucuronoxilomanana en ratones resistentes a la criptococosis

Eosinophils Contribute to IL-4 Production and Shape the T-Helper Cytokine Profile and Inflammatory Response in Pulmonary Cryptococcosis

OX40 Ligation on Activated T Cells Enhances the Control ofCryptococcus neoformansand Reduces Pulmonary Eosinophilia

Contact Info

Product

Resources

About