Genetic Control of the Susceptibility to Bacterial Infection


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Clearly, an analysis of the human genome with respect to variable susceptibility to infection is already beginning to provide important new insights into the mechanisms of human diversity. In considering genetic susceptibility to infectious disease it is important not only to consider the genetic makeup of the host but also that of the infectious agent. Here, we focus mainly on recent studies of the genetic factors that may modify susceptibility to infection in humans and touch only briefly on some recent developments in microbial genetics that may play an important role in this interaction.

Mouse models for studying genetic susceptibility to infection have been reviewed recently elsewhere McLeod et al. The observation that the hemoglobin variants that occur at polymorphic frequencies are unevenly distributed among tropical populations, and the discovery that in every population in which thalassemia is common there is a different pattern of mutation, suggests that these diseases must have arisen independently in different parts of the world and reached their high frequency by locally-acting factors such as selection and drift Flint et al.

Although earlier studies suggesting that the sickle cell trait might be protective against malaria Allison have been confirmed more recently Hill et al. The malaria transmission intensity goes from most intense holoendemic to least intense hypoendemic. Figure adapted with permission from Miller Surveys of malaria prevalence have shown that before eradication campaigns were initiated, the disease was endemic below meters in Papua New Guinea and in parts of Melanesia.

Allen, A. Alexander, M. Alpers, T. Peto, J. Clegg, and D. Weatherall, in prep. Evidence about the possible mechanisms involved has also come recently from studies in Vanuatu Williams et al. It appears that homozygotes are more susceptible to malaria but only at a time when the disease rarely kills. Thus, it is possible that this may provide them with an immunizing dose of malaria that offers later protection. Interestingly, in areas in which both types of malaria occur, the earliest infections in life are usually attributable to P.

Furthemore, there is some evidence that there may be cross-immunization between this form of malaria and that attributable to P. It is now clear that many other red cell polymorphisms have been shaped by malaria.


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The protective effect of a deficiency of the red cell enzyme, glucosephosphate dehydrogenase G6PD , has been confirmed recently by Ruwende et al. Protection is also mediated by variation in the structure or synthesis of a variety of red cell-surface antigens Miller ; the molecular basis for the absence of the Duffy antigen, found many years ago to be associated with resistance to P.

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Genetic Control of the Susceptibility to Bacterial Infection

By gene mapping analysis for the Melanesian form of ovalocytosis, which is sometimes difficult to identify phenotypically, it has been found that this polymorphism provides complete protection against cerebral malaria S. Allen, pers. Work over recent years has shown that genetic variability attributable to selection by malaria is not confined to the red blood cell.

Certain polymorphisms of the HLA—DR system are associated with substantial protection against both cerebral malaria and severe malarial anemia Hill et al. Furthermore, as in the case of the thalassemias, the particular pattern of polymorphisms varies among different populations. Whereas earlier studies of HLA associations with disease viewed the histocompatibility antigens as informative markers for closely linked genes that might encode for genuine immune response determinants, more recent studies at the molecular level have suggested that the class 1 and 2 genes and their products may, in themselves, function as immune response agents through determinant selection.

It is now believed, particularly in the case of the infectious disease associations, that the products of these loci act through differential selection of particular peptide epitopes from a pathogen for presentation to T lymphocytes. Studies of the HLA—B53 association with malaria have provided an excellent example of how this might be mediated through the identification of HLA—B53 cytotoxic lymphocytes that recognize a particular parasite epitope Hill et al.

Another interesting malaria association that has been uncovered recently involves the gene encoding tumor necrosis factor TNF. Reporter gene analysis indicates that this polymorphism can increase levels of TNF expression Wilson et al.

Complex genetic control of susceptibility to malaria in mice | Genes & Immunity

The case of TNF, although compelling, raises a general problem about the application of the genomic approach to the analysis of susceptibility to disease. On one hand, there is a strong clinical association with a candidate gene that is known to be involved in the disease process, and for which there is good evidence that its level of expression is a critical determinant of clinical outcome Tracey On the other hand, the evidence that the polymorphism is functional relies on reporter gene experiments that may or may not be relevant to the in vivo situation.

Attempts to demonstrate that the polymorphism affects the levels of TNF production in blood taken from uninfected individuals have failed Westendorp et al. Furthermore, it is important to prove beyond doubt that a polymorphism, whether functional or not, is the actual cause of the disease association rather than simply a genetic marker.

The TNF gene resides in the class III region of the MHC, densely surrounded by genes of fundamental importance to host defense, so the dissection of disease associations across this region and replication of these associations in different populations will be of great importance. If the high gene frequencies for red cell and other polymorphisms reflect protection against malaria, it is difficult at first sight to understand why they have not become more evenly distributed in the tropical populations of the world.

Why is Melanesian ovalocytosis not more widespread, and why do different HLA—DR polymorphisms appear to be protective in particular populations? It seems likely that these observations reflect the fairly recent appearance of malaria as the principal agent that has maintained these polymorphisms, a notion that is strengthened by an analysis of the relationship between globin gene polymorphisms and their associated restriction fragment length polymorphism haplotypes Flint et al.

They also suggest that malaria must have been a particularly powerful selective force to have recruited so many deleterious traits in such a short time. Although less progress has been made than in the case of malaria, there is increasing evidence that variability in host responsiveness to other parasitic infections may have a strong genetic basis Hill A major recent advance has been the use of segregation and linkage analysis in 11 Brazilian families to localize a gene, termed SM1, that governs intensity of infection by Schistosoma mansoni Marquet et al. It lies at chromosome 5q31—q33, a region encoding interleukin-4 IL-4 , IL-5, and several other immunological mediators that are thought to contribute to host defense in this disease.

The result is of general importance because it illustrates the feasibility of making a genome-wide search to discover critical susceptibility loci for common infections. This is of particular interest because, as in the case of malaria, mucocutaneous leishmaniasis has been found to be accompanied by high circulating levels of TNF. It has been suspected for some time that there may be individual susceptibility to bacterial disease, and progress in investigating this possibility has been increased dramatically by the availability of probes for a wide variety of candidate genes.

The importance of genetic variability in TNF production in response to infection, as noted in the case of malaria, has been further emphasised by the recent observation that TNF promoter polymorphisms are related to susceptibility to some important bacterial infections, notably meningogoccal meningitis Nadel et al. Although it is too early to say precisely how these associations have arisen, it is clear that the further exploration of TNF variants and their receptors in relationship to bacterial disease may play an important role in elucidating the mechanisms of individual susceptibility to these conditions.

The mannose-binding protein MBP , a serum lectin that plays an important role in immunity, is emerging as another interesting candidate. MBP is involved in the activation of complement and acts directly as an opsonin, using the C1q receptor on macrophages.

Microbiology - Bacteria Antibiotic Resistance

Because MBP deficiency has been implicated in an increased susceptibility to bacterial and fungal infections in children, it is clear that the association between these variants and infection is well worth exploring by the analysis of large population samples. It has been suspected for some years that the ability to secrete the soluble forms of the ABO blood group antigens into saliva and other body fluids, which is the secretor status of an individual, may be associated with varying susceptibility to bacterial infection.

Recently, the molecular basis for the nonsecretor phenotype has now been determined Kelly et al. It turns out that nonsecretors are homozygous for a nonsense allele at this locus. It has been found recently that this variant occurs at a high frequency in sub-Saharan Africans, suggesting that it may be the predominant nonsecretor mutation in many populations Hill A five-group system. Leprosy and the human genome. Microbiol Mol Biol Rev 74 4 — Genetics of leprosy reactions: an overview.

Mem Inst Oswaldo Cruz Suppl1 — Leprosy: review of epidemiological, clinical, and etiopathogenic aspects — part1. An Bras Dermatol 89 2 — Comparative genomic and phylogeographic analysis of Mycobacterium leprae. Nat Genet 41 12 —9. Mira MT. Genetic host resistance and susceptibility to leprosy. Microbes Infect 8 4 — Genetics of leprosy: expected-and unexpected-developments and perspectives.

Clin Dermatol 34 1 — Genetic epidemiology of the susceptibility to leprosy. J Clin Invest 79 4 — Chakravartti MR, Vogel F. A twin study on leprosy. Topics in Human Genetics. Stuttgart: Thieme Abel L, Demenais F. Detection of major genes for susceptibility to leprosy and its subtypes in a Caribbean island: Desirade island. Am J Hum Genet 42 2 — PubMed Abstract Google Scholar.

A major gene controls leprosy susceptibility in a hyperendemic isolated population from north of Brazil. J Infect Dis — A major susceptibility locus for leprosy in India maps to chromosome 10p Nat Genet 27 4 — Chromosome 6q25 is linked to susceptibility to leprosy in a Vietnamese population. Nat Genet 33 3 —5. Genomewide association study of leprosy. N Engl J Med 27 — Genome-wide analysis of protein-coding variants in leprosy. J Invest Dermatol — Am J Hum Genet 5 — Human leukocyte antigen class I region single-nucleotide polymorphisms are associated with leprosy susceptibility in Vietnam and India.

J Infect Dis 9 — Leprosy and the adaptation of human toll-like receptor 1. PLoS Pathog 6 7 :e J Infect Dis 11 —7. Role of tumor necrosis factor-alpha and interleukin promoter gene polymorphisms in leprosy. J Infect Dis 11 — Interleukin promoter single-nucleotide polymorphisms as markers for disease susceptibility and disease severity in leprosy.

Genes Immun 5 7 —5. IL promoter single nucleotide polymorphisms are significantly associated with resistance to leprosy.

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Hum Genet 2 — Association of IL10 polymorphisms and leprosy: a meta-analysis. PLoS One 10 9 :e Am J Hum Genet 91 5 — Nat Genet 43 12 — BMC Infect Dis 14 1 Association between killer-cell immunoglobulin-like receptor genotypes and leprosy in Brazil. Tissue Antigens — Discovery of six new susceptibility loci and analysis of pleiotropic effects in leprosy. Nat Genet 47 3 — Hum Genet 12 — PLoS One 8 8 :e Genes Immun 16 2 —9. Stepwise replication identifies a low-producing lymphotoxin-alpha allele as a major risk factor for early-onset leprosy.

Nat Genet 39 4 — Genetic and functional analysis of common MRC1 exon 7 polymorphisms in leprosy susceptibility.

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Hum Genet 3 — Nature — PLoS Genet 9 7 :e Linkage disequilibrium pattern and age-at-diagnosis are critical for replicating genetic associations across ethnic groups in leprosy. Hum Genet 1 — Toll-like receptor 1 Ns single-nucleotide polymorphism is associated with leprosy risk and regulates immune activation during mycobacterial infection. J Infect Dis 1 —9. Toll-like receptor 2 TLR2 polymorphisms are associated with reversal reaction in leprosy.

Genetic Control of Natural Resistance to Infection and Malignancy

J Infect Dis 2 — J Infect Dis 8 — Association of TNFSF8 regulatory variants with excessive inflammatory responses but not leprosy per se. J Infect Dis 6 — Biomed Res Int Genetic polymorphisms of the IL6 and NOD2 genes are risk factors for inflammatory reactions in leprosy. Human NOD2 recognizes structurally unique muramyl dipeptides from Mycobacterium leprae. Infect Immun 84 9 — Lancet — IL suppresses antimicrobial activity in human leprosy. J Invest Dermatol 10 —7.

LRRK2 transport is regulated by its novel interacting partner Rab PLoS One 9 10 :e J Immunol 9 — LRRK2 is a negative regulator of Mycobacterium tuberculosis phagosome maturation in macrophages. Malaria in humans: Plasmodium falciparum blood infection levels are linked to chromosome 5qq33 Am J Hum Genet 63 : — Heritability and segregation analysis of immune responses to specific malaria antigens in Papua New Guinea Genet Epidemiol 17 : 16— Familial correlation of immunoglobulin G subclass responses to Plasmodium flaciparum antigens in Burkina Faso Infect Immun 69 : — Genetic regulation of fever in Plasmodium falciparum malaria in Gambian twin children J Infect Dis : — Genetic linkage of mild malaria to the major histocompatibility complex in Gambian children: study of affected sibling pairs BMJ : 96— Cellular mechanism for the protective effect of haemoglobin S against P.

Common west African HLA antigens are associated with protection from severe malaria Nature : — Morbidity and severity of malaria attacks in carriers of sickle-cell trait Rev Epidemiol Sante Publique 40 : — Transgenic mice expressing human sickle hemoglobin are partially resistant to rodent malaria Blood 81 : — High incidence of malaria in alpha-thalassaemic children Nature : — Weatherall DJ.

Phenotype-genotype relationships in monogenic disease: lessons from the thalassaemias Nat Rev Genet 2 : — Natural selection of hemi- and heterozygotes for G6PD deficiency in Africa by resistance to severe malaria Nature : — Haplotype diversity and linkage disequilibrium at human G6PD: recent origin of alleles that confer malarial resistance Science : — Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation Proc Natl Acad Sci USA 94 : — Variation in the TNF-alpha promoter region associated with susceptibility to cerebral malaria Nature : — Severe malarial anemia annd cerebral malaria are associated with different tumor necrosis factor promoter alleles J Infect Dis : — Natural resistance to infection with intracellular parasites: isolation of a candidate for Bcg Cell 73 : — Susceptibility to mouse cytomegalovirus is associated with deletion of an activating natural killer cell receptor of the C-type lectin superfamily Nat Genet 28 : 42— Vital involvement of a natural killer cell activation receptor in resistance to viral infection Science : — Taylor-Robinson AW.

Regulation of immunity to malaria: valuable lessons learned from murine models Parasitol Today 11 : — Stevenson MM, Skamene E. Modulation of primary antibody responses to sheep erythrocytes in Plasmodium chabaudi -infected resistant and susceptible mouse strains Infect Immun 54 : — Role of macrophage-derived nitric oxide in suppression of lymphocyte proliferation during blood-stage malaria J Leukoc Biol 58 : 23— Plasmodium chabaudi: a rodent malaria model for in-vivo and in-vitro cytoadherence of malaria parasites in the absence of knobs Parasite Immunol 9 : — Differences in susceptibility of various mouse strains to haemoprotozoan infections: possible correlation with natural killer activity Parasite Immunol 2 : — Murine malaria: genetic control of resistance to Plasmodium chabaudi Infect Immun 38 : 80— Role of mononuclear phagocytes in elimination of Plasmodium chabaudi AS infection Parasite Immunol 11 : — Meding SJ, Langhorne J.

Granulocyte-macrophage colony-stimulating factor-deficient mice have impaired resistance to blood-stage malaria Infect Immun 69 : — Su Z, Stevenson MM. Central role of endogenous gamma interferon in protective immunity against blood-stage Plasmodium chabaudi AS infection Infect Immun 68 : — Deficiency in tumor necrosis factor alpha activity does not impair early protective Th1 responses against blood-stage malaria Infect Immun 67 : — Involvement of macrophage scavenger receptors in protection against murine malaria Am J Trop Med Hyg 59 : — Mouse loci for malaria-induced mortality and the control of parasitaemia letter Nat Genet 17 : — Resistance to Plasmodium chabaudi in B10 mice: influence of the H-2 complex and testosterone Infect Immun 56 : — Genetic control of blood parasitaemia in mouse malaria maps to chromsome 8 letter Nat Genet 17 : — Plasmodium chabaudi AS: erythropoietic responses during infection in resistant and susceptible mice Exp Parasitol 75 : — Differential induction of helper T cell subsets during blood-stage Plasmodium chabaudi AS infection in resistant and susceptible mice Clin Exp Immunol 92 : 77— A Th1-associated increase in tumor necrosis factor alpha expression in the spleen correlates with resistance to blood-stage malaria in mice Infect Immun 64 : — Role of endogenous gamma interferon in host response to infection with blood-stage Plasmodium chabaudi AS Infect Immun 58 : — Temporal expression of an H2-linked locus in host response to mouse malaria Immunogenetics 50 : — A role for macrophage scavenger receptors in atherosclerosis and susceptibility to infection Nature : — Identification and characterization of naturally occurring variants of the macrophage scavenger receptor SR-A Mamm Genome 11 : — Demant P, Hart AA.

Recombinant congenic strains — a new tool for analyzing genetic traits determined by more than one gene Immunogenetics 24 : — Genetic control of resistance to Listeria monocytogenes: regulation of leukocyte inflammatory responses by the Hc locus J Immunol : — Inflammatory response and resistance to Listeria monocytogenes J Immunol : — Targeted disruption of the p50 subunit of NF-kappa B leads to multifocal defects in immune responses Cell 80 : — The murine mutation osteopetrosis is in the coding region of the macrophage colony stimulating factor gene Nature : — Guleria I, Pollard JW.

Aberrant macrophage and neutrophil population dynamics and impaired Th1 response to Listeria monocytogenes in colony-stimulating factor 1-deficient mice Infect Immun 69 : — Conditional vascular cell adhesion molecule 1 deletion in mice. Impaired lymphocyte migration to bone marrow J Exp Med : — Testosterone-induced abrogation of self-healing of Plasmodium chabaudi malaria in B10 mice: mediation by spleen cells Infect Immun 59 : — Flint J, Mott R.

Finding the molecular basis of quantitative traits: successes and pitfalls Nat Rev Genet 2 : — Download references.


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  7. Correspondence to P Gros. Reprints and Permissions. EBioMedicine Experimental Animals Journal of Neuroinflammation Malaria Journal Clinical and Experimental Nephrology Advanced search. Skip to main content. Abstract Malaria is a major infectious disease worldwide, with over 1 million deaths in African children every year. Introduction Malaria, caused by mosquito-borne hematoprotozoan parasites of the genus Plasmodium , is endemic in more than 90 countries, and together with HIV and tuberculosis constitutes one of the major causes of death by infectious diseases worldwide.

    Genetic factors in susceptibility to malaria in humans A large body of evidence has accumulated over the past 50 years to indicate that genetic factors can influence the onset, progression, severity of disease, and ultimate outcome of malaria infection in man.

    A mouse model of malaria infection The genetic component of susceptibility to malaria is acknowledged to be complex in humans. Strain variations in susceptibility When infected with strains of P.

    Genetic Control of the Susceptibility to Bacterial Infection Genetic Control of the Susceptibility to Bacterial Infection
    Genetic Control of the Susceptibility to Bacterial Infection Genetic Control of the Susceptibility to Bacterial Infection
    Genetic Control of the Susceptibility to Bacterial Infection Genetic Control of the Susceptibility to Bacterial Infection
    Genetic Control of the Susceptibility to Bacterial Infection Genetic Control of the Susceptibility to Bacterial Infection
    Genetic Control of the Susceptibility to Bacterial Infection Genetic Control of the Susceptibility to Bacterial Infection
    Genetic Control of the Susceptibility to Bacterial Infection Genetic Control of the Susceptibility to Bacterial Infection
    Genetic Control of the Susceptibility to Bacterial Infection Genetic Control of the Susceptibility to Bacterial Infection
    Genetic Control of the Susceptibility to Bacterial Infection Genetic Control of the Susceptibility to Bacterial Infection
    Genetic Control of the Susceptibility to Bacterial Infection Genetic Control of the Susceptibility to Bacterial Infection

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