title: Host ICAMs play a role in cell invasion by Mycobacterium tuberculosis and Plasmodium falciparum.
abstract: Intercellular adhesion molecules (ICAMs) belong to the immunoglobulin superfamily and participate in diverse cellular processes including host-pathogen interactions. ICAM-1 is expressed on various cell types including macrophages, whereas ICAM-4 is restricted to red blood cells. Here we report the identification of an 11-kDa synthetic protein, M5, that binds to human ICAM-1 and ICAM-4, as shown by in vitro interaction studies, surface plasmon resonance and immunolocalization. M5 greatly inhibits the invasion of macrophages and erythrocytes by Mycobacterium tuberculosis and Plasmodium falciparum, respectively. Pharmacological and siRNA-mediated inhibition of ICAM-1 expression also results in reduced M. tuberculosis invasion of macrophages. ICAM-4 binds to P. falciparum merozoites, and the addition of recombinant ICAM-4 to parasite cultures blocks invasion of erythrocytes by newly released merozoites. Our results indicate that ICAM-1 and ICAM-4 play roles in host cell invasion by M. tuberculosis and P. falciparum, respectively, either as receptors or as crucial accessory molecules.
authors.affiliation: Recombinant Gene Products Group, International Centre for Genetic Engineering and Biotechnology, ICGEB, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Kuhulika
authors.initials: K
authors.lastname: Bhalla
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology, ICGEB, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Monika
authors.initials: M
authors.lastname: Chugh
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology, ICGEB, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Sonali
authors.initials: S
authors.lastname: Mehrotra
authors.affiliation: Department of Biotechnology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India.
authors.forename: Sumit
authors.initials: S
authors.lastname: Rathore
authors.affiliation: Immunology Group, International Centre for Genetic Engineering and Biotechnology, ICGEB, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Sultan
authors.initials: S
authors.lastname: Tousif
authors.affiliation: Immunology Group, International Centre for Genetic Engineering and Biotechnology, ICGEB, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Ved
authors.initials: V
authors.lastname: Prakash Dwivedi
authors.affiliation: Recombinant Gene Products Group, International Centre for Genetic Engineering and Biotechnology, ICGEB, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Prem
authors.initials: P
authors.lastname: Prakash
authors.affiliation: Recombinant Gene Products Group, International Centre for Genetic Engineering and Biotechnology, ICGEB, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Sachin
authors.initials: S
authors.lastname: Kumar Samuchiwal
authors.affiliation: Recombinant Gene Products Group, International Centre for Genetic Engineering and Biotechnology, ICGEB, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Sushil
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Recombinant Gene Products Group, International Centre for Genetic Engineering and Biotechnology, ICGEB, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Dhiraj
authors.initials: D
authors.lastname: Kumar Singh
authors.affiliation: Immunology Group, International Centre for Genetic Engineering and Biotechnology, ICGEB, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Swapnil
authors.initials: S
authors.lastname: Ghanwat
authors.affiliation: Immunology Group, International Centre for Genetic Engineering and Biotechnology, ICGEB, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Dhiraj
authors.initials: D
authors.lastname: Kumar
authors.affiliation: Immunology Group, International Centre for Genetic Engineering and Biotechnology, ICGEB, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Gobardhan
authors.initials: G
authors.lastname: Das
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology, ICGEB, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Asif
authors.initials: A
authors.lastname: Mohmmed
authors.affiliation: Malaria Group, International Centre for Genetic Engineering and Biotechnology, ICGEB, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Pawan
authors.initials: P
authors.lastname: Malhotra
authors.affiliation: Recombinant Gene Products Group, International Centre for Genetic Engineering and Biotechnology, ICGEB, Aruna Asaf Ali Marg, New Delhi 110067, India.
authors.forename: Anand
authors.initials: A
authors.lastname: Ranganathan
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D004912:Erythrocytes / Q000469:parasitology; D005260:Female; D054884:Host-Pathogen Interactions; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000737:chemistry / Q000378:metabolism*; D016778:Malaria, Falciparum / Q000469:parasitology; D052940:Merozoites / Q000502:physiology; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000235:genetics / Q000502:physiology*; D010963:Plasmodium falciparum / Q000502:physiology*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D014376:Tuberculosis / Q000382:microbiology; D020798:Two-Hybrid System Techniques
chemical_list: D015815:Cell Adhesion Molecules; C095100:ICAM4 protein, human; D018799:Intercellular Adhesion Molecule-1